(2-Acetamidyl)thio-beta-D-galactopyranoside derivatives

Abstract

The present invention is 1 , R 1 , R 2a , R 2b and R 3 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] TIFF2022543859000114.tif59165

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 among different organs. Depending on its extracellular or intracellular localization, it can exhibit a wide range of biological functions, including 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 neoplasia 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 shown to play a key role 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 Clin. 2018,14(1):75-92; DeRoo EP. et al., Blood. 201 5, 125(11):1813-21) and cardiovascular diseases (Zhong X. et al. Clin Exp Pharmacol Physiol. 2019, 46(3):197-203). Circulating 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, which contain at least the essential substituent R 1 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. Summary of the Invention

[0010] The present invention provides novel compounds of formula (I) 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.

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

[0012] [ka] (In the formula, R 1 teeth, - structure:

[0013] [ka] represents an amide group; -- R N11 teeth, --- -C 1-6 -alkyl; --- -CH2-CH2-OC 1-3 -alkyl; --- -CH2-C 1-3 -fluoroalkyl (in particular -CH2-CF3 or -CH2-C(CH3)2F); --- -C 0-2 -Alkylene-C 3-6 -cycloalkyl, 3-6 -cycloalkyl is unsubstituted or substituted by 1 or 2 fluoro or methyl; 0-2 -Alkylene-C 3-6 -cycloalkyl; --- -C 0-2 -Alkylene-C 4-6 -cycloalkyl, 4-6 -cycloalkyl has one oxygen ring atom, -C 0-2 -Alkylene-C 4-6 -cycloalkyl; --- -CH2-CH2-NR N21 R N22 (R N21 and R N22 together with the nitrogen atom to which they are attached, form a 4- to 6-membered heterocyclyl (particularly morpholin-4-yl) selected from azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl and morpholin-4-yl; or --- -C 1-2 -Alkylene-R 11 (R 11 represents phenyl or 5- or 6-membered heteroaryl (especially thiophenyl, pyridinyl, imidazolyl), which phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted by one methyl; will be replaced. ); --- phenyl or 5- or 6-membered heteroaryl (especially pyridinyl), which phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted by one methyl; or

[0014] [ka] represents; And R N12 is hydrogen or C 1-2 - represents alkyl; -- or R N11 and R N12 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl selected from azetidin-1-yl, pyrrolidin-1-yl and piperidin-1-yl, which 4- to 6-membered heterocyclyl is independently unsubstituted or substituted with 1 or 2 substituents which are independently methyl or fluoro; -- or R N11 and R N12 together with the nitrogen atom to which they are attached form morpholin-4-yl; -- or R N11 and RN12 together with the nitrogen atom to which they are attached form a partially aromatic bicyclic ring consisting of pyrrolidin-1-yl or piperidin-1-yl, the pyrrolidine or piperidine being fused to a phenyl ring; (particularly, the bicyclic ring is indolin-1-yl); 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 thiazolyl or pyridinyl), which 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1 or 2 substituents independently selected from halogen, methyl, cyano and methoxy; represents; - R 2a represents hydrogen; and R 2b teeth, -- -C 2-4 -Alkyl (especially ethyl); -- -C 0-1 -Alkylene-Ar 2b (Ar 2b represents phenyl or 5- or 6-membered heteroaryl (especially 1H-pyrazol-3-yl), where the phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1 or 2 methyl; represents; - or R 2a and R 2b each represents hydrogen, methyl, ethyl or n-propyl; - or R 2a and R 2b along with the carbon atoms to which they are attached. -- C 3-6 -Cycloalkylene (the C 3-6 -cycloalkylene is independently an unsubstituted substituted or substituted with 1 or 2 substituents, each of which is independently methyl or fluoro; - tetrahydro-2H-pyran-4,4-diyl, which is unsubstituted or substituted by 2 or 4 methyl; or - piperidine-4,4-diyl, pyrrolidine-3,3-diyl or azetidine-3,3-diyl, in which the piperidine, pyrrolidine or azetidine nitrogens are independently unsubstituted or -C 1-3 -Alkyl, -C 0-2 -Alkylene-C 3-6 -cycloalkyl or -LR N2 ( ----L- is -CO-, -SO2-, * -CO-NH-, * -CO-O- or * -SO2-NH-, --- R N2 -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 -CO-O-methyl); (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 2a and R 2b are the structures (S 2AB) spiro-bicyclic ring system

[0015] [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 3 is hydroxy or C 1-3 -Alkoxy (especially methoxy).

[0016] 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.

[0017] 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, and in particular essentially pure, enantiomer form. Similarly, it is understood that a particular asymmetric center of a compound may be in the (R)- or (S)-configuration, or , in a particular relative configuration, such description is understood to mean said compound in enriched, and in particular essentially pure, form with respect to each configuration of said asymmetric centers.

[0018] 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).

[0019] 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.

[0020] 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), (II) and (III) 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.

[0021] In this application, bonds drawn as dotted lines indicate the point of attachment of the depicted group. For example, the group

[0022] [ka] is an azetidine-1-carbonyl group.

[0023] 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.

[0024] 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.

[0025] 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. Examples of references include "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.

[0026] The definitions set forth herein are uniformly applied to the compounds of formula (I) defined in any one of embodiments 1) to 19) 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.

[0027] 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:

[0028] [ka] can be named (2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-phenyl-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-thiyl or, alternatively, 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 (S)-2-(1-(cyclopropylsulfonyl)-4-hydroxypiperidin-4-yl)-2-(((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)-N-ethyl-N-methylacetamide is also understood to be: 1,3-di-deoxy-1-((2-(1-(cyclopropylsulfonyl)-4-hydroxypiperidin-4-yl)-N-ethyl-N-methylacetamide)-(S)-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside.

[0029] Whenever a substituent is described as optional, such substituent may be absent (i.e., the respective residue is unsubstituted with respect to such optional substituent), in which case all sites having a free valence (e.g., in an aromatic ring, ring carbon atoms and / or ring nitrogen atoms having a free valence to which such optional substituent may be attached) may be optionally replaced by hydrogen. It is understood that each of the optional heteroatoms is substituted with . Similarly, when the term "optionally" is used in reference to a (ring) heteroatom, this term means that each of the optional heteroatoms is not present (i.e., a group has no heteroatoms / is a carbocyclic ring / etc.) or that each of the optional heteroatoms is present as expressly defined. Unless expressly defined otherwise in each embodiment or claim, the groups defined herein are unsubstituted.

[0030] The term "halogen" means fluorine, chlorine or bromine, preferably fluorine or chlorine.

[0031] 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. R N11 "-C 1-6 When "-alkyl" appears, this term preferably denotes methyl, ethyl, isopropyl, isobutyl, pent-3-yl, 2,2-dimethyl-propyl or 3,3-dimethyl-butyl.

[0032] "-C x-y The term "-alkylene-", used alone or in combination, refers to a bivalently bound alkyl group, as defined above, having x to y carbon atoms. 0-y The term "-alkylene-" refers to 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 the 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 that substituent is C 1-y - means that the group is attached to the remainder of the molecule via an alkylene group or that it is directly attached to the remainder of the molecule (i.e., 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-.

[0033] 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.

[0034] 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-yThe term "fluoroalkyl" (x and y are each integers) refers to a fluoroalkyl group as defined above having x to y carbon atoms. For example, C 1-3 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.

[0035] 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.

[0036] 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.

[0037] "C with ring oxygen atom x-y The term "cycloalkyl" refers to a cycloalkyl group as defined above having x to y carbon atoms, x-y - means a cycloalkyl group in which one ring carbon atom of the cycloalkyl is replaced by an oxygen atom. Such groups are unsubstituted or substituted as expressly defined. Examples are, inter alia, oxetanyl, tetrahydrofuranyl and tetrahydropyranyl. 4-6 -cycloalkyl, 3-6 -Cycloalkyl has one ring oxygen atom, 4-6 -cycloalkyl" is tetrahydro-2H-pyran-4-yl.

[0038] "-C x-y The 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 2a and R 2b 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 specifically 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, 3,3-difluorocyclobutane-1,1-diyl, 4,4-dimethylcyclohexane-1,1-diyl or 4,4-difluorocyclohexane-1,1-diyl; in particular 4,4-difluorocyclohexane-1,1-diyl.

[0039] 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 3 "C 1-3 When expressing "-alkoxy", this term preferably means methoxy or ethoxy, in particular methoxy.

[0040] The term "heterocyclyl" is used unless expressly defined broader or narrower. "C", whether used alone or in combination, means a saturated or unsaturated non-aromatic monocyclic hydrocarbon ring having 1 or 2 ring heteroatoms independently selected from nitrogen, sulfur and oxygen (in particular, 1 oxygen atom, 1 sulfur atom, 1 nitrogen atom, 2 nitrogen atoms, 2 oxygen atoms, 1 nitrogen atom and 1 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.

[0041] The term "aryl", used alone or in combination, means phenyl or naphthyl, preferably phenyl, said aryl groups being unsubstituted or substituted as expressly defined.

[0042] 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 substituent R representing "5- or 6-membered heteroaryl" 11 In the context of R, this term especially means thiophenyl, pyridinyl, imidazolyl; more especially thiophen-2-yl, pyridin-2-yl, 1H-imidazol-4-yl. N11 When Ar represents "5- or 6-membered heteroaryl", this term refers to the above groups, in particular pyridinyl; especially pyridin-2-yl or pyridin-3-yl; the 5- or 6-membered heteroaryl group is unsubstituted or substituted as expressly defined. 1When represents "5- or 6-membered heteroaryl", this term refers to the above groups, in particular pyridinyl or thiazolyl; especially thiazol-2-yl or pyridin-3-yl; said 5- or 6-membered heteroaryl group is unsubstituted or substituted as expressly defined.

[0043] R 2a and R 2b However, together with the carbon atoms to which they are attached, they are called "structures (S 2AB ) spiro-bicyclic ring system, such a structure (S 2AB ) specifically means the following structure:

[0044] [ka] The term "cyano" refers to the group --CN.

[0045] 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)-.

[0046] "R N11 and R N12 together with the nitrogen atom to which they are attached form a partially aromatic bicyclic ring consisting of pyrrolidin-1-yl or piperidin-1-yl, the pyrrolidine or piperidine being fused to a phenyl ring. Examples of bicyclic rings in which the pyrrolidine or piperidine are fused to a phenyl ring are indolin-1-yl, isoindolin-2-yl, 3,4-dihydroisoquinolin-2(1H)-yl and 3,4-dihydroquinolin-1(2H)-yl, especially indolin-1-yl.

[0047] "R N11 and R N12together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl selected from azetidin-1-yl, pyrrolidin-1-yl and piperidin-1-yl, which 4- to 6-membered heterocyclyl is independently unsubstituted or substituted by 1 or 2 substituents, which substituents are independently methyl or fluoro, examples of heterocyclyl are in particular azetidin-1-yl which is unsubstituted or substituted in the 2- or 3-position by one methyl or substituted in the 3-position by two fluoro; pyrrolidin-1-yl which is unsubstituted or substituted in the 3-position by two fluoro; piperidin-1-yl which is unsubstituted or substituted in the 3- or 4-position by two fluoro.

[0048] 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.

[0049] 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.

[0050] Further aspects of the invention are described below: 2) The second aspect is a compound represented by the formula (I S ) which is also a compound of formula (I) according to embodiment 1):

[0051] [ka] (In the formula, the group R 1 The carbon atom to which is bonded is represented by formula (I S ) [i.e., in the absolute (S)-configuration]; R 1 , R 2a , R 2b , R 3 and Ar 1 is as defined in embodiment 1.

[0052] 3) In another embodiment, Ar 1 represents phenyl substituted with 1, 2 or 3 substituents, said substituents being 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 a meta-substituent is present, said meta-substituent is preferably halogen; It relates to compounds according to embodiment 1) or 2).

[0053] 4) Another embodiment is 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).

[0054] 5) In another embodiment, Ar 1 The structure:

[0055] [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

[0056] 6) In another embodiment, Ar 1 The structure:

[0057] [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

[0058] 7) In another embodiment, Ar 1 but:

[0059] [ka] relates to compounds according to embodiment 1) or 2).

[0060] In a subembodiment of embodiment 7), Ar 1 represents 3,4,5-trifluorophenyl.

[0061] 8) In another embodiment, R 1 But the structure

[0062] [ka] represents an amide group; - R N11 but, -- -C 1-6 - alkyl (in particular methyl, ethyl, isobutyl, 2,2-dimethylprop-1-yl or 3,3-dimethylbut-1-yl); -- -CH2-CH2-OC 1-3 -alkyl; -- -CH2-C 1-3 -fluoroalkyl (in particular -CH2-CF3 or -CH2-C(CH3)2F); --cyclopropyl, cyclobutyl, -CH2-cyclopropyl, -CH2-cyclopentyl, -CH2-1-fluorocyclopentyl or -CH2-CH2-cyclopropyl; -- 3,3-difluorocyclobutyl, -CH2-3,3-difluorocyclobutyl or 4,4-dimethylcyclohexyl; ---CH2-tetrahydro-2H-pyran-4-yl or -CH2-CH2-tetrahydro-2H-pyran-4-yl; -- tetrahydro-2H-pyran-4-yl or oxetan-3-yl; ---CH2-CH2-morpholin-4-yl; or ---CH2-thiophenyl, -CH2-pyridinyl, benzyl or -CH2-1-methyl-1H-imidazol-4-yl; -- phenyl or pyridinyl; or

[0063] [ka] and R N12 is hydrogen or C 1-2 - represents alkyl (especially methyl); - or RN11 and R N12 together with the nitrogen atom to which they are attached form a 4-6 membered heterocyclyl selected from: azetidin-1-yl, unsubstituted or substituted in the 2- or 3-position by one methyl or substituted in the 3-position by two fluoro; pyrrolidin-1-yl, unsubstituted or substituted in the 3-position by two fluoro; and piperidin-1-yl, unsubstituted or substituted in the 3- or 4-position by two fluoro or methyl; - or R N11 and R N12 together with the nitrogen atom to which they are attached form morpholin-4-yl; - or R N11 and R N12 together with the nitrogen atom to which they are attached form an indolin-1-yl, isoindolin-2-yl, 3,4-dihydroisoquinolin-2(1H)-yl or 3,4-dihydroquinolin-1(2H)-yl ring (especially indolin-1-yl); The compounds according to the embodiments 1) to 7).

[0064] 9) In another aspect, R 1 But the structure

[0065] [ka] represents an amide group; - R N11 but, -- -C 1-6 - alkyl (in particular methyl, ethyl, isobutyl, 2,2-dimethylprop-1-yl or 3,3-dimethylbut-1-yl); -- -CH2-C 1-3 -fluoroalkyl (in particular -CH2-CF3 or -CH2-C(CH3)2F); --cyclopropyl, cyclobutyl, -CH2-cyclopropyl, -CH2-cyclopentyl, -CH2-1-fluorocyclopentyl or -CH2-CH2-cyclopropyl; -- -CH2-3,3-difluorocyclobutyl; ---CH2-tetrahydro-2H-pyran-4-yl or -CH2-CH2-tetrahydro-2H-pyran-4-yl; -- tetrahydro-2H-pyran-4-yl or oxetan-3-yl; -- Benzyl; -- phenyl or pyridinyl; or

[0066] [ka] and R N12 is hydrogen or C 1-2 - represents alkyl (especially methyl); - or R N11 and R N12 together with the nitrogen atom to which they are attached form a 4-6 membered heterocyclyl selected from azetidin-1-yl, unsubstituted or substituted at the 3-position by two fluoro; pyrrolidin-1-yl, unsubstituted or substituted at the 3-position by two fluoro; and piperidin-1-yl, unsubstituted or substituted at the 3- or 4-position by two fluoro; or R N11 and R N12 together with the nitrogen atom to which they are attached form morpholin-4-yl; - or R N11 and R N12 but together with the nitrogen atom to which they are attached form an indolin-1-yl ring; The compounds according to the embodiments 1) to 7).

[0067] 10) In another aspect, R 1 But the structure

[0068] [ka] represents an amide group; - R N11 but, -- -C 1-6- alkyl (in particular methyl, ethyl, isobutyl, 2,2-dimethylprop-1-yl or 3,3-dimethylbut-1-yl); -- -CH2-CH2-OC 1-3 -alkyl; -- -CH2-C 1-3 -fluoroalkyl (in particular -CH2-CF3 or -CH2-C(CH3)2F); --cyclopropyl, cyclobutyl, -CH2-cyclopropyl, -CH2-cyclopentyl, -CH2-1-fluorocyclopentyl or -CH2-CH2-cyclopropyl; -- 3,3-difluorocyclobutyl or -CH2-3,3-difluorocyclobutyl; ---CH2-tetrahydro-2H-pyran-4-yl or -CH2-CH2-tetrahydro-2H-pyran-4-yl; -- tetrahydro-2H-pyran-4-yl or oxetan-3-yl; ---CH2-CH2-morpholin-4-yl; ---CH2-thiophenyl, -CH2-pyridinyl, benzyl or -CH2-1-methyl-1H-imidazol-4-yl; or -- phenyl or pyridinyl; represents; R N12 is hydrogen or C 1-2 - alkyl (especially methyl); The compounds according to the embodiments 1) to 7).

[0069] 11) In another aspect, R 1 But the structure

[0070] [ka] represents an amide group; - R N11 but, -- -C 1-6 - alkyl (in particular methyl, ethyl, isobutyl, 2,2-dimethylprop-1-yl or 3,3-dimethylbut-1-yl); -- -CH2-CH2-OC 1-3 -alkyl; -- -CH2-C 1-3 -fluoroalkyl (in particular -CH2-CF3 or -CH2-C(CH3)2F); or --cyclopropyl, cyclobutyl, -CH2-cyclopropyl, -CH2-cyclopentyl, -CH2-1-fluorocyclopentyl or -CH2-CH2-cyclopropyl; represents; R N12 C 1-2 - alkyl (especially methyl); The compounds according to the embodiments 1) to 7).

[0071] 12) In another aspect, R 1 but:

[0072] [ka]

[0073] [ka] With respect to the compounds according to embodiments 1) to 7), each of the above groups A) to C) forms a specific sub-embodiment; another sub-embodiment relates to groups A) and / or B).

[0074] 13) Another aspect is - R 2a represents hydrogen; and R 2b but, -- -C 2-4 -Alkyl (especially ethyl); -- Benzyl; phenyl, unsubstituted or substituted by one or two methyl groups; or -- 5-membered heteroaryl (especially 1H-pyrazol-3-yl), which is unsubstituted or substituted by one methyl; represents; - or R 2a and R 2beach represents methyl, ethyl or n-propyl; - or R 2a and R 2b 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, 3,3-difluorocyclobutane-1,1-diyl, 4,4-difluorocyclohexane-1,1-diyl; or, in addition, 4,4-dimethylcyclohexane-1,1-diyl); -- tetrahydro-2H-pyran-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); -- Azetidine-3,3-diyl (the nitrogen of the azetidine is -CO-OC 1-3 -substituted by alkyl (especially -CO-O-methyl); or forming a 3- to 6-membered ring selected from - R 2a and R 2b along with the carbon atoms to which they are attached, giving the structure:

[0075] [ka] forming a spiro-bicyclic ring system of; The compound according to any one of the embodiments 1) to 12).

[0076] 14) In another aspect, R 2a represents hydrogen; R 2b but, - -C 2-4 -Alkyl (especially ethyl); - Benzyl; phenyl, unsubstituted or substituted by one or two methyl groups; or - 5-membered heteroaryl (especially 1H-pyrazol-3-yl), which is unsubstituted or substituted by one methyl; Represents; The compound according to any one of the embodiments 1) to 12).

[0077] 15) In another aspect, R 2a and R 2b each represents methyl, ethyl or n-propyl (especially methyl); relates to a compound according to any one of embodiments 1) to 12).

[0078] 16) In another aspect, R 2a and R 2b 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, 3,3-difluorocyclobutane-1,1-diyl, 4,4-difluorocyclohexane-1,1-diyl; or, in addition, 4,4-dimethylcyclohexane-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 (in particular tetrahydro-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 by 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:

[0079] 17) In another aspect, R 3 represents methoxy; relates to compounds according to any one of embodiments 1) to 16).

[0080] 18) In another aspect, R 3 represents hydroxy; according to any one of embodiments 1) to 16), The present invention relates to a compound having the formula:

[0081] 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+8+3+2+1、14+8+4+1、14+8+4+2+1、14+8+5+1、14+8+5+2+1、14+8+6+1、14+8+6+2+1、14+8+7+1、14+8+7+2+1、14+9+1、14+9+2+1、14+9+3+1、14+9+3+2+1、14+9+4+1、14+9+4+2+1、14+9+5+1、14+9+5+2+1、14+9+6+1、14+9+6+2+1、14+9+7+1、14+9+7+2+1、14+10+1、14+10+2+1、14+10+3+1、14+10+3+2+1、14+10+4+1、14+10+4+2+1、14+10+5+1、14+10+5+2+1、14+10+6+1、14+10+6+2+1、14+10+7+1、 14+10+7+2+1、14+11+1、14+11+2+1、14+11+3+1、14+11+3+2+1、14+11+4+1、14+11+4+2+1、14+11+5+1、14+11+5+2+1、14+11+6+1、14+11+6+2+1、14+11+7+1、14+11+7+2+1、14+12+1、14+12+2+1、14+12+3+1、14+12+3+2+1、14+12+4+1、14+12+4+2+1、14+12+5+1、14+12+5+2+1、14+12+6+1、14+12+6+2+1、14+12+7+1、14+12+7+2+1、15+1、15+2+1、15+3+1、15+3+2+1、15+4+1、15+4+2+1、15+5+1、15+5+2+1、15+6+1、15+6+2+1、15+7+1、15+7+2+1、15+8+1、15+8+2+1、15+8+3+1、15+8+3+2+1、15+8+4+1、15+8+4+2+1、15+8+5+1、15+8+5+2+1、15+8+6+1、15+8+6+2+1、15+8+7+1、15+8+7+2+1、15+9+1、15+9+2+1、15+9+3+1、15+9+3+2+1、15+9+4+1、15+9+4+2+1、15+9+5+1、15+9+5+2+1、15+9+6+1、15+9+6+2+1、15+9+7+1、15+9+7+2+1、15+10+1、15+10+2+1、15+10+3+1、15+10+3+2+1、15+10+4+1、15+10+4+2+1、15+10+5+1、15+10+5+2+1、15+10+6+1、15+10+6+2+1、15+10+7+1、15+10+7+2+1、15+11+1、15+11+2+1、15+11+3+1、15+11+3+2+1、15+11+4+1、15+11+4+2+1、15+11+5+1、15+11+5+2+1、15+11+6+1、15+11+6+2+1、15+11+7+1、15+11+7+2+1、15+12+1、15+12+2+1、15+12+3+1、15+12+3+2+1、15+12+4+1、15+12+4+2+1、15+12+5+1、15+12+5+2+1、15+12+6+1、15+12+6+2+1、15+12+7+1、15+12+7+2+1、 16+1、16+2+1、16+3+1、16+3+2+1、16+4+1、16+4+2+1、16+5+1、16+5+2+1、16+6+1、16+6+2+1、16+7+1、16+7+2+1、16+8+1、16+8+2+1、16+8+3+1、16+8+3+2+1、16+8+4+1、16+8+4+2+1、16+8+5+1、16+8+5+2+1、16+8+6+1、16+8+6+2+1、16+8+7+1、16+8+7+2+1、16+9+1、16+9+2+1、16+9+3+1、16+9+3+2+1、16+9+4+1、16+9+4+2+1、16+9+5+1、16+9+5+2+1、16+9+6+1、16+9+6+2+1、16+9+7+1、16+9+7+2+1、16+10+1、16+10+2+1、16+10+3+1、16+10+3+2+1、16+10+4+1、16+10+4+2+1、16+10+5+1、16+10+5+2+1、16+10+6+1、16+10+6+2+1、16+10+7+1、16+10+7+2+1、16+11+1、16+11+2+1、16+11+3+1、16+11+3+2+1、16+11+4+1、16+11+4+2+1、16+11+5+1、16+11+5+2+1、16+11+6+1、16+11+6+2+1、16+11+7+1、16+11+7+2+1、16+12+1、16+12+2+1、16+12+3+1、16+12+3+2+1、16+12+4+1、16+12+4+2+1、16+12+5+1、16+12+5+2+1、16+12+6+1、16+12+6+2+1、16+12+7+1、16+12+7+2+1、17+1、17+2+1、17+3+1、17+3+2+1、17+4+1、17+4+2+1、17+5+1、17+5+2+1、17+6+1、17+6+2+1、17+7+1、17+7+2+1、17+8+1、17+8+2+1、17+8+3+1、17+8+3+2+1、17+8+4+1、17+8+4+2+1、17+8+5+1、17+8+5+2+1、17+8+6+1、17+8+6+2+1、17+8+7+1、17+8+7+2+1、17+9+1、17+9+2+1、17+9+3+1、17+9+3+2+1、17+9+4+1、17+9+4+2+1、17+9+5+1、17+9+5+2+1、17+9+6+1。、17+9+6+2+1、17+9+7+1、17+9+7+2+1、17+10+1、17+10+2+1、17+10+3+1、17+10+3+2+1、17+10+4+1、17+10+4+2+1、17+10+5+1、17+10+5+2+1、17+10+6+1、17+10+6+2+1、17+10+7+1、17+10+7+2+1、17+11+1、17+11+2+1、17+11+3+1、17+11+3+2+1、17+11+4+1、17+11+4+2+1、17+11+5+1、17+11+5+2+1、17+11+6+1、17+11+6+2+1、17+11+7+1、17+11+7+2+1、17+12+1、17+12+2+1、17+12+3+1、17+12+3+2+1、17+12+4+1、17+12+4+2+1、17+12+5+1、17+12+5+2+1、17+12+6+1、17+12+6+2+1、17+12+7+1、17+12+7+2+1、17+13+1、17+13+2+1、17+13+3+1、17+13+3+2+1、17+13+4+1、17+13+4+2+1、17+13+5+1、17+13+5+2+1、17+13+6+1、17+13+6+2+1、17+13+7+1、17+13+7+2+1、17+13+8+1、17+13+8+2+1、17+13+8+3+1、17+13+8+3+2+1、17+13+8+4+1、17+13+8+4+2+1、17+13+8+5+1、17+13+8+5+2+1、17+13+8+6+1、17+13+8+6+2+1、17+13+8+7+1、17+13+8+7+2+1、17+13+9+1、17+13+9+2+1、17+13+9+3+1、17+13+9+3+2+1、17+13+9+4+1、17+13+9+4+2+1、17+13+9+5+1、17+13+9+5+2+1、17+13+9+6+1、17+13+9+6+2+1、17+13+9+7+1、17+13+9+7+2+1、17+13+10+1、17+13+10+2+1、17+13+10+3+1、17+13+10+3+2+1、17+13+10+4+1、17+13+10+4+2+1、17+13+10+5+1、17+13+10+5+2+1、17+13+10+6+1、17+13+10+6+2+1、17+13+10+7+1、17+13+10+7+2+1、17+13+11+1、17+13+11+2+1、17+13+11+3+1、17+13+11+3+2+1、17+13+11+4+1、17+13+11+4+2+1、17+13+11+5+1、17+13+11+5+2+1、17+13+11+6+1、17+13+11+6+2+1、17+13+11+7+1、17+13+11+7+2+1、17+13+12+1、17+13+12+2+1、17+13+12+3+1、17+13+12+3+2+1、17+13+12+4+1、17+13+12+4+2+1、17+13+12+5+1、17+13+12+5+2+1、17+13+12+6+1、17+13+12+6+2+1、17+13+12+7+1、17+13+12+7+2+1、 17+14+1、17+14+2+1、17+14+3+1、17+14+3+2+1、17+14+4+1、17+14+4+2+1、17+14+5+1、17+14+5+2+1、17+14+6+1、17+14+6+2+1、17+14+7+1、17+14+7+2+1、17+14+8+1、17+14+8+2+1、17+14+8+3+1、17+14+8+3+2+1、17+14+8+4+1、17+14+8+4+2+1、17+14+8+5+1、17+14+8+5+2+1、17+14+8+6+1、17+14+8+6+2+1、17+14+8+7+1、17+14+8+7+2+1、17+14+9+1、17+14+9+2+1、17+14+9+3+1、17+14+9+3+2+1、17+14+9+4+1、17+14+9+4+2+1、17+14+9+5+1、17+14+9+5+2+1、17+14+9+6+1、17+14+9+6+2+1、17+14+9+7+1、17+14+9+7+2+1、17+14+10+1、17+14+10+2+1、17+14+10+3+1、17+14+10+3+2+1、17+14+10+4+1、17+14+10+4+2+1、17+14+10+5+1、17+14+10+5+2+1、17+14+10+6+1、17+14+10+6+2+1、17+14+10+7+1、17+14+10+7+2+1、17+14+11+1、17+14+11+2+1、17+14+11+3+1、17+14+11+3+2+1、17+14+11+4+1、17+14+11+4+2+1、17+14+11+5+1、17+14+11+5+2+1、17+14+11+6+1、17+14+11+6+2+1、17+14+11+7+1、17+14+11+7+2+1、17+14+12+1、17+14+12+2+1、17+14+12+3+1、17+14+12+3+2+1、17+14+12+4+1、17+14+12+4+2+1、17+14+12+5+1、17+14+12+5+2+1、17+14+12+6+1、17+14+12+6+2+1、17+14+12+7+1、17+14+12+7+2+1、17+15+1、17+15+2+1、17+15+3+1、17+15+3+2+1、17+15+4+1、17+15+4+2+1、17+15+5+1、17+15+5+2+1、17+15+6+1、17+15+6+2+1、17+15+7+1、17+15+7+2+1、17+15+8+1、17+15+8+2+1、17+15+8+3+1、17+15+8+3+2+1、17+15+8+4+1、17+15+8+4+2+1、17+15+8+5+1、17+15+8+5+2+1、17+15+8+6+1、17+15+8+6+2+1、17+15+8+7+1、17+15+8+7+2+1、17+15+9+1、17+15+9+2+1、17+15+9+3+1、17+15+9+3+2+1、17+15+9+4+1、17+15+9+4+2+1、17+15+9+5+1、17+15+9+5+2+1、17+15+9+6+1、17+15+9+6+2+1、17+15+9+7+1、17+15+9+7+2+1、17+15+10+1、17+15+10+2+1、17+15+10+3+1、17+15+10+3+2+1、17+15+10+4+1、17+15+10+4+2+1、17+15+10+5+1、17+15+10+5+2+1、17+15+10+6+1、17+15+10+6+2+1、17+15+10+7+1、17+15+10+7+2+1、17+15+11+1、17+15+11+2+1、17+15+11+3+1、17+15+11+3+2+1、17+15+11+4+1、17+15+11+4+2+1、17+15+11+5+1、17+15+11+5+2+1、17+15+11+6+1、17+15+11+6+2+1、17+15+11+7+1、17+15+11+7+2+1、17+15+12+1、17+15+12+2+1、17+15+12+3+1、17+15+12+3+2+1、17+15+12+4+1、17+15+12+4+2+1、17+15+12+5+1、17+15+12+5+2+1、17+15+12+6+1、17+15+12+6+2+1、17+15+12+7+1、17+15+12+7+2+1、 17+16+1、17+16+2+1、17+16+3+1、17+16+3+2+1、17+16+4+1、17+16+4+2+1、17+16+5+1、17+16+5+2+1、17+16+6+1、17+16+6+2+1、17+16+7+1、17+16+7+2+1、17+16+8+1、17+16+8+2+1、17+16+8+3+1、17+16+8+3+2+1、17+16+8+4+1、17+16+8+4+2+1、17+16+8+5+1、17+16+8+5+2+1、17+16+8+6+1、17+16+8+6+2+1、17+16+8+7+1、17+16+8+7+2+1、17+16+9+1、17+16+9+2+1、17+16+9+3+1、17+16+9+3+2+1、17+16+9+4+1、17+16+9+4+2+1、17+16+9+5+1、17+16+9+5+2+1、17+16+9+6+1、17+16+9+6+2+1、17+16+9+7+1、17+16+9+7+2+1、17+16+10+1、17+16+10+2+1、17+16+10+3+1、17+16+10+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.

[0082] 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+9+5+1" means embodiment 13) which is dependent on embodiment 9) which is dependent on embodiment 5) which is dependent on embodiment 1), i.e. embodiment "13+9+5+1" corresponds to a compound of formula (I) according to embodiment 1) further limited by all the features of embodiments 5), 9) and 13).

[0083] 20) Another embodiment relates to compounds of formula (I) according to embodiment 1), which are selected from the following compounds: (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide; 2-(((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-hydroxy-N,N,3-trimethylbutanamide; 2-(((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)-N,N-diethyl-3-hydroxy-3-methylbutanamide; 2-(((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-hydroxy-3-methyl-1-(2-methylazetidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-3-methyl-1-(3-methylazetidin-1-yl)butan-1-one; 1-(azetidin-1-yl)-2-(((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-hydroxy-3-methylbutan-1-one; 2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-N-isobutyl-N-methylacetamide;2-(((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)-N-ethyl-2-(4-hydroxy-1-methylpiperidin-4-yl)-N-methylacetamide; N-benzyl-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-N-methylacetamide; 2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-1-(piperidin-1-yl)ethan-1-one; 2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-1-(indolin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N,N-dimethylacetamide; 2-(((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)-N,N-diethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; 2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(2-methylazetidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(3-methylazetidin-1-yl)ethan-1-one; 1-(azetidin-1-yl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)ethan-1-one; (S)-N-benzyl-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(piperidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(indolin-1-yl)ethan-1-one; 2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(pyrrolidin-1-yl)ethan-1-one; (S)-N-(cyclopentylmethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; 2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; 2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-((1-methyl-1H-imidazol-4-yl)methyl)acetamide; 2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)acetamide; N-(2-cyclopropylethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-(cyclopropylmethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; 2-(((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)-N-ethyl-2-(1-hydroxycyclohexyl)-N-methylacetamide; 2-(((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-(1-hydroxycyclohexyl)-1-(piperidin-1-yl)ethan-1-one; (R)-2-(((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-(1-hydroxycyclohexyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(((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-(1-hydroxycyclohexyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; N-cyclobutyl-2-(((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-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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)-N-(2-fluoro-2-methylpropyl)-2-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclohexyl)-N-methyl-N-(pyridin-2-ylmethyl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N,N-dimethylacetamide;2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-ethyl-N-methylacetamide; (S)-N-Cyclobutyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-1-(piperidin-1-yl)ethan-1-one; (S)-N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(2-fluoro-2-methylpropyl)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-((1-fluorocyclopentyl)methyl)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(3,3-dimethylbutyl)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(3,3-difluoroazetidin-1-yl)-2-(((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)ethan-1-one; 1-(azetidin-1-yl)-2-(((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-(1-hydroxycyclopentyl)ethan-1-one; 2-(((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-(1-hydroxycyclopentyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; N-Cyclobutyl-2-(((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-(1-hydroxycyclopentyl)-N-methylacetamide; 2-(((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-(1-hydroxycyclopentyl)-N-methyl-N-neopentylacetamide; (S)-2-(((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)-N-ethyl-2-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclobutyl)-1-(piperidin-1-yl)ethan-1-one; (S)-N-(cyclopropylmethyl)-2-(((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-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclobutyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(((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)-N-(2-fluoro-2-methylpropyl)-2-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclobutyl)-N-methyl-N-neopentylacetamide; (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)-N-ethyl-N-methylacetamide; (S)-N-(cyclopropylmethyl)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)-N-methylacetamide; (S)-2-(((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)-N,3-diethyl-3-hydroxy-N-methylpentanamide; N-benzyl-2-(((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-hydroxy-N,3-dimethylbutanamide; 2-(((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-hydroxy-3-methyl-1-(piperidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-3-methyl-1-(pyrrolidin-1-yl)butan-1-one; 2-(((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-hydroxy-N,3-dimethyl-N-((1-methyl-1H-imidazol-4-yl)methyl)butanamide; N-(cyclopropylmethyl)-2-(((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-hydroxy-N,3-dimethylbutanamide; 2-(((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-hydroxy-N-(2-methoxyethyl)-N,3-dimethylbutanamide; 2-(((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-hydroxy-N,3-dimethyl-N-(2-morpholinoethyl)butanamide; 2-(((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)-N-ethyl-3-hydroxy-N-methylpentanamide; N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methylpentanamide; 2-(((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)-N-ethyl-3-hydroxy-N-methyl-4-phenylbutanamide; N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-4-phenylbutanamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-N-methylacetamide; (S)-2-(1-(cyclopropylsulfonyl)-4-hydroxypiperidin-4-yl)-2-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxyphenyl) hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-N-methylacetamide; N-cyclopropyl-4-(1-(((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-(ethyl(methyl)amino)-2-oxoethyl)-4-hydroxypiperidine-1-carboxamide; and Methyl 4-((S)-1-(((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-(ethyl(methyl)amino)-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate.

[0084] 21) Another embodiment relates to compounds of formula (I) according to embodiment 1), which are selected from the following compounds: (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide; (S)-2-(((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-hydroxy-N,N,3-trimethylbutanamide; (S)-2-(((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)-N-ethyl-3-hydroxy-N,3-dimethylbutanamide; (S)-2-(((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)-N,N-diethyl-3-hydroxy-3-methylbutanamide; (S)-2-(((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-hydroxy-3-methyl-1-((R)-2-methylazetidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-3-methyl-1-((S)-2-methylazetidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-3-methyl-1-(3-methylazetidin-1-yl)butan-1-one; (S)-1-(azetidin-1-yl)-2-(((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-pi ran-2-yl)thio)-3-hydroxy-3-methylbutan-1-one; (S)-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-N-isobutyl-N-methylacetamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxy-1-methylpiperidin-4-yl)-N-methylacetamide; (S)-N-benzyl-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-1-(piperidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-1-(indolin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N,N-dimethylacetamide; (S)-2-(((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)-N,N-diethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-((R)-2-methylazetidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-((S)-2-methylazetidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(3-methylazetidine -1-yl)ethan-1-one; (S)-1-(azetidin-1-yl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)ethan-1-one; (S)-N-benzyl-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(piperidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(indolin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(thiophen-2-ylmethyl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(pyrrolidin-1-yl)ethan-1-one; (S)-N-(cyclopentylmethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-((1-methyl) ethyl-1H-imidazol-4-yl)methyl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)acetamide; (S)-N-(2-cyclopropylethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-(cyclopropylmethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(((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)-N-ethyl-2-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclohexyl)-1-(piperidin-1-yl)ethan-1-one; (S)-2-(((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-(1-hydroxycyclohexyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-N-Cyclobutyl-2-(((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-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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)-N-(2-fluoro-2-methylpropyl)-2-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclohexyl)-N-methyl-N-(pyridin-2-ylmethyl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N,N-dimethylacetamide;(S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-ethyl-N-methylacetamide; (S)-N-Cyclobutyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-1-(piperidin-1-yl)ethan-1-one; (S)-N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-N-Cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(2-fluoro-2-methylpropyl)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-((1-fluorocyclopentyl)methyl)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(3,3-dimethylbutyl)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluoro Phenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)ethan-1-one; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(3,3-difluoroazetidin-1-yl)-2-(((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)ethan-1-one; (S)-2-(((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)-N-ethyl-2-(1-hydroxycyclopentyl)-N-methylacetamide; (S)-1-(azetidin-1-yl)-2-(((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-(1-hydroxycyclopentyl)ethan-1-one; (S)-2-(((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-(1-hydroxycyclopentyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-N-Cyclobutyl-2-(((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-(1-hydroxycyclopentyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclopentyl)-N-methyl-N-neopentylacetamide; (S)-2-(((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)-N-ethyl-2-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-1-(azetidin-1-yl)-2-(((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-(1-hydroxycyclobutyl)ethan-1-one; (S)-2-(((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-(1-hydroxycyclobutyl)-1-(piperidin-1-yl)ethan-1-one; (S)-N-(cyclopropylmethyl)-2-(((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-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclobutyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(((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)-N-(2-fluoro-2-methylpropyl)-2-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclobutyl)-N-methyl-N-neopentylacetamide; (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)-N-ethyl-N-methylacetamide; (S)-1-(azetidin-1-yl)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)ethan-1-one; (S)-N-(cyclopropylmethyl)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)-N-methylacetamide; (S)-2-(((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)-N,3-diethyl-3-hydroxy-N-methylpentanamide; (S)-N-(cyclopropylmethyl)-2-(((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-ethyl-3-hydroxy-N-methylpentanamide; (S)-2-(((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-ethyl-N-(2-fluoro-2-methylpropyl)-3-hydroxy-N-methylpentanamide; (S)-N-benzyl-2-(((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-hydroxy-N,3-dimethylbutanamide; (S)-2-(((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-hydroxy-3-methyl-1-(piperidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-3-methyl-1-(pyrrolidin-1-yl)butan-1-one; (S)-2-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxyphenyl) hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-hydroxy-N,3-dimethyl-N-((1-methyl-1H-imidazol-4-yl)methyl)butanamide; (S)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N,3-dimethylbutanamide; (S)-2-(((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-hydroxy-N,3-dimethyl-N-neopentylbutanamide; (S)-2-(((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-hydroxy-N-(2-methoxyethyl)-N,3-dimethylbutanamide; (S)-2-(((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-hydroxy-N,3-dimethyl-N-(2-morpholinoethyl)butanamide; (2S,3R)-2-(((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)-N-ethyl-3-hydroxy-N-methylpentanamide; (2S,3S)-2-(((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)-N-ethyl-3-hydroxy-N-methylpentanamide; (2S,3R)-1-(azetidin-1-yl)-2-(((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-hydroxypentan-1-one; (2S,3S)-1-(azetidin-1-yl)-2-(((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-hydroxypentan-1-one; (2S,3R)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methylpentanamide; (2S,3S)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methylpentanamide; (2S,3R)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-4-phenylbutanamide; (2S,3S)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-4-phenylbutanamide; (2S,3R)-1-(azetidin-1-yl)-2-(((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-hydroxy-4-phenylbutan-1-one; (2S,3S)-1-(azetidin-1-yl)-2-(((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-hydroxy-4-phenylbutan-1-one; (2S,3R)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-4-phenylbutanamide; (2S,3S)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-4-phenylbutanamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-N-methylacetamide; (S)-2-(1-(cyclopropylsulfonyl)-4-hydroxypiperidin-4-yl)-2-(((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)-N-ethyl-N-methylacetamide; and Methyl 4-((S)-1-(((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-(ethyl(methyl)amino)-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate.

[0085] 22) In addition to the compounds described in embodiment 20), further compounds according to embodiment 1) are selected from the following compounds: (S)-2-(((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)-N-ethyl-3-hydroxy-N,3-dimethylbutanamide; and (S)-N-Cyclopropyl-4-(1-(((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-(ethyl(methyl)amino)-2-oxoethyl)-4-hydroxypiperidine-1-carboxamide.

[0086] 23) In addition to the compounds described in embodiment 21), further compounds according to embodiment 1) are selected from the following compounds: (2S,3R)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; (2S,3S)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; (2S,3R)-1-1-(azetidin-1-yl)-2-(((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-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)propan-1-one; (2S,3S)-1-(azetidin-1-yl)-2-(((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-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)propan-1-one; (2S,3R)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; (2S,3S)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; and (S)-N-Cyclopropyl-4-(1-(((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-(ethyl(methyl)amino)-2-oxoethyl)-4-hydroxypiperidine-1-carboxamide.

[0087] 24) In addition to the compounds described in embodiment 20), further compounds according to embodiment 1) are selected from the following compounds: N-(cyclopropylmethyl)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(oxetan-3-yl)acetamide; (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-2-(ethyl(methyl)amino)-1-(3-hydroxy-1-(methoxycarbonyl)azetyl)- (4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate; N-cyclopropyl-4-((S)-2-(ethyl(methyl)amino)-1-(((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-oxoethyl)-4-hydroxypiperidine-1-carboxamide; 2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-phenylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-phenylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(pyridin-2-yl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(pyridin-3-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(pyridin-2-yl)acetamide; N-cyclobutyl-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; N-cyclobutyl-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)acetamide; (R)-N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((2S,3R,4S,5R,6R)-5-hydro 6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; N-benzyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-N-((3,3-difluorocyclobutyl)methyl)-N-ethyl-2-(((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)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-(tetrahydro-2H-pyran-4-yl)acetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; N-ethyl-2-(((2S,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromothiazol-2-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide;2-(((2S,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl) 2-(((2S,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide;2-(((2S,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; 2-(((2S,3R,4S,5R,6R)-4-(4-(3-cyano-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; N-ethyl-2-(((2S,3R,4S,5R,6R)-4-(4-(3-fluoro-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide;(R)-N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((2S,3R,4S,5R,6R)-4-(4-(6-fluoro-5-methylpyridin-3-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-methylacetamide; (S)-N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((2S,3R,4S,5R,6R)-4-(4-(6-fluoro-5-methylpyridin-3-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(2-fluoro-2-methylpropyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N,N-dimethylacetamide;2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-isopropyl-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-dimethylbutyl)-2-(((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)-N-methylacetamide; N-(2-cyclopropylethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-difluorocyclobutyl)-2-(((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)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(oxetan-3-yl)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-1-morpholinoethan-1-one; 2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-dimethylpiperidin-1-yl)-2-(((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)ethan-1-one; N-(bicyclo[1.1.1]pentan-1-yl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(tetrahydro-2H-pyran-4-yl)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(pentan-3-yl)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-isopropylacetamide;2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-difluorocyclobutyl)-2-(((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)acetamide; 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(2,2,2-trifluoroethyl)acetamide; 1-(4,4-difluoropiperidin-1-yl)-2-(((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-(6-hydroxyspiro[2.5]octan-6-yl)ethan-1-one; 1-(4,4-difluoropiperidin-1-yl)-2-(1-hydroxy-4,4-dimethylcyclohexyl)-2-(((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)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(7-hydroxyspiro[3.5]nonan-7-yl)ethan-1-one; 1-(4,4-difluoropiperidin-1-yl)-2-(((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-(7-hydroxy-2-oxaspiro[3.5]nonan-7-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(8-hydroxyspiro[4.5]decan-8-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(9-hydroxy-3-oxaspiro[5.5]undecan-9-yl)ethan-1-one; 1-(4,4-difluoropiperidin-1-yl)-2-(4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(((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)ethan-1-one; 2-(1,1-difluoro-6-hydroxyspiro[2.5]octan-6-yl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; and 2-(4,4-Difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((2S,3R,4S,5R,6R)-3-ethoxy-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)ethan-1-one.

[0088] 25) In addition to the compounds described in embodiment 21), further compounds according to embodiment 1) are selected from the following compounds: (S)-N-(cyclopropylmethyl)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(oxetan-3-yl)acetamide; (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-2-(ethyl(methyl)amino)-1-(3-hydroxy-1-(methoxycarbonyl)azetidin-3-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyrazor benzoyl diacetate; N-cyclopropyl-4-((S)-2-(ethyl(methyl)amino)-1-(((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-oxoethyl)-4-hydroxypiperidine-1-carboxamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-phenylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-phenylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(pyridin-2-yl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(pyridin-3-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(pyridin-2-yl)acetamide; (S)-N-cyclobutyl-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; (S)-N-Cyclobutyl-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)acetamide; (S)-N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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-pyrazol-1-yl) (2-yl)thio)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; (S)-N-benzyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-((3,3-difluorocyclobutyl)methyl)-N-ethyl-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-(tetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-ethyl-2-(((2S,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromothiazol-2-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3-cyano-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-ethyl-2-(((2S,3R,4S,5R,6R)-4-(4-(3-fluoro-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((2S,3R,4S,5R,6R)-4-(4-(6-fluoro-5-methylpyridin-3-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(2-fluoro-2-methylpropyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; (S)-N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N,N-dimethylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-isopropyl-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-dimethylbutyl)-2-(((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)-N-methylacetamide; (S)-N-(2-cyclopropylethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-difluorocyclobutyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(oxetan-3-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-1-morpholinoethan-1-one; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-dimethylpiperidin-1-yl)-2-(((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)ethan-1-one; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(4,4-dimethylcyclohexyl)-2-(((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)-N-methylacetamide; (S)-N-(bicyclo[1.1.1]pentan-1-yl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(tetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(pentan-3-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-isopropylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-dimethylbutyl)-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-difluorocyclobutyl)-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(4,4-dimethylcyclohexyl)-2-(((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)acetamide; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(6-hydroxyspiro[2.5]octan-6-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(1-hydroxy-4,4-dimethylcyclohexyl)-2-(((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)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(7-hydroxyspiro[3.5]nonan-7-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(7-hydroxy-2-oxaspiro[3.5]nonan-7-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(8-hydroxyspiro[4.5]decan-8-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(9-hydroxy-3-oxaspiro[5.5]undecan-9-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(((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)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(((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)ethan-1-one; (2S)-2-(1,1-difluoro-6-hydroxyspiro[2.5]octan-6-yl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; and (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((2S,3R,4S,5R,6R)-3-ethoxy-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)ethan-1-one.

[0089] The compounds of formula (I) according to embodiments 1) to 25) and their pharma- ceutically acceptable salts can be used as medicaments, for example in the form of pharmaceutical compositions for enteral (such as, in particular orally, for example in the form of tablets or capsules) or parenteral (including topical application or inhalation) administration.

[0090] 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.

[0091] 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.

[0092] 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.

[0093] 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.

[0094] 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.

[0095] 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, in particular idiopathic pulmonary fibrosis (also called cryptogenic fibrosing alveolitis); systemic inflammatory diseases such as rheumatoid arthritis, scleroderma (systemic sclerosis, SSc), lupus (systemic lupus erythematosus, SLE), polymyositis or mixed connective tissue disease (MCTD); All forms of lung / pulmonary fibrosis, including pulmonary fibrosis secondary to pulmonary fibrosis; 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; all forms of heart / cardiac fibrosis, including cardiac fibrosis associated with diabetes, 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; - caused by / associated with heart disease (also called cardiorenal syndrome type 1 and type 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 type 1 or 2), or caused by / associated with inflammatory diseases and disorders (such as glomerulonephritis and systemic inflammatory diseases such as SLE or SSc, tubulointerstitial nephritis, vasculitis, sepsis, glomerulonephritis secondary to urinary tract infection), or caused by / associated with polycystic kidney disease, or caused by / associated with obstructive nephropathy (including stones, benign prostatic hyperplasia, prostate cancer, retroperitoneal pelvic tumors), or caused by / associated with neurogenic bladder Acute kidney injury and chronic kidney disease (CKD) (in particular stages 1 to 5 CKD as defined in the Kidney Disease Improving Global Outcomes (KDIGO) Guidelines) resulting from / associated with chronic kidney disease-related symptoms, in particular (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 due to / associated with CKD (stages 1-5 as defined by the Cardiovascular Outcomes and Global Outcomes (KDIGO) Guidelines); rheumatic heart disease due to / associated with bacterial infection; cardiac and vascular tumors; cardiomyopathies and arrhythmias; valvular heart disease (including valvular calcification and degenerative aortic stenosis); inflammatory heart disease due to / associated with infection, carditis, glomerulonephritis, cancer; heart failure (HF) defined as including congestive HF, particularly including 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.

[0096] 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.

[0097] 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.

[0098] 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).

[0099] 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.

[0100] 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.

[0101] 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.

[0102] 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.

[0103] 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.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] 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.

[0110] 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 group, R 1 , R 2a , R 2b , R 3 and Ar 1 is as defined for formula (I). Other abbreviations used herein are either explicitly defined or as defined in the experimental section. In some cases, the generic group, R 1 , R 2a , R 2b , R 3 and Ar 1may 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.

[0111] 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 the compounds of formula (I) are described.

[0112] [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, which is: is reacted with 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 isopropylidene, benzylidene or bis(phenyl)-2-phenylpropane. R can be protected by a cyclic protecting group such as 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 the 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 or LiOH. 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, in methanol, ethyl acetate, THF, etc. or mixtures thereof, or with BBr3 in a solvent such as DCM. When Pg represents 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 If it is, then the compound of structure 3 can be deprotected under acidic conditions using acetic acid or aqueous TFA.

[0113] [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 by the reaction of glucofuranose (glucofuranose) with methods known to those skilled in the art. It can be produced in three steps from furanose (Carbohydrate Research 1994, 251, 33-67).

[0114] [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 n-BuLi in a solvent such as THF, diethyl ether, toluene, etc. at low temperature (Chem Lett 1977, 471-474). In structure 6, the term Pg represents a suitable protecting group for thiols, such as acyl or tetrahydropyran. When such a protecting group represents an acyl protecting group, such protecting group can be removed by reaction of the compound of structure 6 with the compound of structure 7 under standard conditions, for example in the presence or absence of an additional solvent such as THF, dioxane, and in the presence of NaOH, LiOH, or 25% NH It can be cleaved with water or alcohol in the presence of a base such as 4OH. If such a protecting group represents a tetrahydropyran group, it 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 by using a combination of boron trifluoride, 2-mercaptoethanol in a solvent such as DCM (Chem Lett 1996, 999-1000).

[0115] [ka] When Rc is an ester group, compounds of structure 2 can also be prepared from compounds of structure 6A, without the need for a protecting group for the thiol (Chem Lett 1977, 471-474). Compounds of structure 7 and compounds of structure 6A are commercially available.

[0116] [ka] Compounds of structure 3 can be obtained by reacting compounds of structure 8 with compounds of structure 7 in the presence of a strong base such as LDA or n-BuLi in a solvent such as THF, diethyl ether, toluene, etc. at low temperatures such as -78°C (Chem Lett 1977, 471-474).

[0117] [ka] Compounds of structure 8 can be synthesized by reacting compounds of structure 1 with compounds of structure 9 under conditions previously described for the reaction of compounds of structure 2 and structure 3, for example, under phase transfer catalysis conditions in the presence of tetrabutylammonium bromide or tetrabutylammonium hydrogen sulfate and a base such as Na2CO3 (Chem.Comm. 2006, 2379), or under anhydrous conditions in the presence of NaH in THF or DMF. Compounds of structure 9 are commercially available.

[0118] 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.

[0119] Experimental section The following examples illustrate the invention but do not in any way limit its scope.

[0120] 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 (Bruker 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).

[0121] Abbreviations (as used herein): ABTS 2,2'-azino-bis(3-ethylbenzothiazoline-6 -Sulfonic Acid AcOH Acetic acid 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 EtI Ethyl iodide E. coli. Escherichia coli EDC HCl N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide Hydrochloride 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 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(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 TBAHS Tetrabutylammonium hydrogen sulfate 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 TMS-SMe Trimethyl(methylthio)silane TMSOTf Trimethylsilyl trifluoromethanesulfonate T3P Propylphosphonic anhydride t R retention time

[0122] 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).

[0123] 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):

[0124] [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):

[0125] [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):

[0126] [Table 3] D) 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, 5μm. 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.

[0127] The column type, B solvent and run length are noted for each epimer mixture in the corresponding table.

[0128] E) Chiral analytical HPLC (E): Chiralpak 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=MeOH. The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 10% solvent B and 90% solvent A. Detection: 210 nm.

[0129] F) Chiral analytical HPLC (F): Chiralcel OJ-H, 5 μm, 4.6x250mm column thermostated at 40° C. The two elution solvents were as follows: Solvent A=CO2; Solvent B=MeOH. Eluent Flow rate: 4.0 mL / min for 5 min. Elution: isocratic, 15% solvent B and 85% solvent A. Detection: ELSD.

[0130] G) Chiral analytical HPLC (G): ChiralPak IC, 5 μm, 4.6×250 mm column, thermostated at 40° C. The two elution solvents were as follows: Solvent A=CO2; Solvent B=EtOH. The eluent flow rate was 4.0 mL / min for 5 min. Elution: isocratic, 35% solvent B and 65% solvent A. Detection: 210 nm.

[0131] H) Chiral analytical HPLC (H): 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=MeOH. The eluent flow rate is 4.0 mL / min over 3.5 min. Elution: isocratic, 15% solvent B and 85% solvent A. Detection: 210 nm.

[0132] J) Chiral analytical HPLC(J): 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=MeCN / EtOH (1 / 1). The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 20% solvent B and 80% solvent A. Detection: 210 nm.

[0133] K) Chiral analytical HPLC (K): 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 5 min. Elution: isocratic, 30% solvent B and 70% solvent A. Detection: 210 nm.

[0134] Non-chiral preparative methods used: Purification by preparative LC-MS is performed using the conditions described below.

[0135] L) 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):

[0136] [Table 4] M) 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):

[0137] [Table 5] Chiral preparative HPLC method used: Separation of the epimers is achieved by preparative chiral column chromatography using the conditions described below.

[0138] N) Chiral Preparative HPLC (I): A ChiralPack OJ-H, 5 μm, 30x250 mm, thermostated at 40° C. is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeOH. The eluent flow rate is 160 mL / min. Elution is performed with 90% Solvent A and 10% Solvent B. Injection V=2.5 mL, 10 mg / mL MeOH.

[0139] O) Chiral Preparative HPLC (II): A ChiralPack OJ-H, 5 μm, 30x250 mm, thermostated at 40° C. is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeOH. The eluent flow rate is 160 mL / min. Elution is performed with 85% Solvent A and 15% Solvent B. Injection V=1.0 mL, 5 mg / mL MeOH.

[0140] P) Chiral Preparative HPLC (III): A ChiralPack IC, 5 μm, 30x250 mm, thermostated at 40° C. is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=EtOH. The eluent flow rate is 160 mL / min. Elution is performed with 65% Solvent A and 35% Solvent B. Injection V=1.0 mL, 10 mg / mL EtOH.

[0141] Q) Chiral Preparative HPLC (IV): A ChiralCel OJ-H, 5 μm, 30x250 mm, thermostated at 40° C. is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeOH. The eluent flow rate is 160 mL / min. The elution is performed with 85% Solvent A and 15% Solvent B. Injection V=3.5 mL.

[0142] R) Chiral Preparative HPLC (V): A ChiralPack IH, 5 μm, 30x250 mm, thermostated at 40° C. is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeCN / EtOH (1 / 1). The eluent flow rate is 160 mL / min. Elution is performed with 80% solvent A and 20% solvent B. Injection V=2.0 mL, 8 mg / mL, MeCN / EtOH=1 / 1.

[0143] S) Chiral Preparative HPLC (VI): A ChiralCel OJ-H, 5 μm, 30x250 mm, thermostated at 40° C. is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeCN / EtOH (1 / 1). The eluent flow rate is 160 mL / min. Elution is performed with 70% Solvent A and 30% Solvent B. Injection V=3.5 mL.

[0144] Preparation of intermediates For the synthesis of the compounds the following intermediates are prepared:

[0145] Intermediate 1 (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate is synthesized from (3aR,5S,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol according to the literature procedure from Ref: Carbohydrate Research 1994, 251, 33-67 and references cited therein.

[0146] 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. 1 H 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).

[0147] 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 (11.4 g, 28.3 mmol) in DMF (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 (15 to 50% EA), 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=11.4Hz, 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).

[0148] Intermediate 4 1-((3R,4S,5R,6R)-2-Bromo-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl) tetrahydro-2H-pyran-4-yl)-4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-(methylthio)tetrahydro-2H-pyran-3,5-diyl diacetate TMS-SMe (2.2 mL, 15.3 mmol, 2.85 eq) and molecular sieves (4 Å, 4.0 g) are added to a solution of intermediate 1 (2.0 g, 5.4 mmol) in DCM (26.0 mL) at rt. TMS-OTf (0.9 mL, 4.9 mmol, 0.9 eq) is added and the solution is stirred at rt for 17 h. The reaction mixture is quenched with 5% aqueous Na2CO3 (10.0 mL) and stirred at rt for 2 h before adding DCM (10.0 mL) and some water. The phases are separated and the aqueous phase is extracted with DCM (1x10.0 mL). The combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo to recover the crude product which is purified by silica gel column chromatography (18x2.5cm, product added to isolute, 13mL fraction, Hept / EA 99 / 1 to 3 / 7, Rf(Hept / EA 1 / 1)=0.62) to give the title compound (1.7g, 89%) as white crystals; LC-MS: R =0.86min, [M+1” + = None; 1 H NMR (400MHz, CDCl3) δ:5.48(d, J=3.3Hz, 1H), 5.24(t, J=10.0Hz, 1H), 4.38(d, J=9.8Hz, 1H), 4.1-4.17(m, 2H), 3.94(td, J1=6.5H) z, J2=1.1Hz, 1H), 3.69(dd, J1=10.1Hz, J2=3.3Hz, 1H), 2.21(s, 3H), 2.19(s, 3H), 2.18(s, 3H), 2.09(s, 3H).

[0149] 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 (7.5 g, 20.7 mmol) in DMF (140.0 mL) is added 3,4,5-trifluorophenylacetylene (5.0 g, 31 mmol, 1.5 eq), CuI (1.18 g, 6.2 mmol, 0.3 eq) and DIPEA (10.6 mL, 62.0 mmol, 3.0 eq). The reaction mixture is stirred at 45 °C for 17 h, then cooled to rt, diluted with EA and filtered. The organic layer is washed with aq.sat.NH4Cl, brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product as a beige solid. The crude material is purified by Flash Master (ISCO, 120 g column, flow rate 85 mL / min, Hept / EA 40 / 640 to 0 / 100, Rf(Hept / EA 1 / 1)=0.29, UV active and stained with KMnO4) to recover the desired product as a white powder (9.2 g, 86%). LC-MS: R =1.0min, [M+1 ”+ =518.09. 1 H NMR (400MHz, CDCl3) δ:7.81(s, 1H), 7.44(m, 2H), 5.77(dd, J1=9.5Hz, J2=11.0Hz), 5.63(d, J=3.3Hz) , 5.19(dd, J1=11.1Hz, J2=3.2Hz, 1H), 4.59(d, J=9.5Hz, 1H), 4.18(m, 3H), 2.29( s, 3H), 2.09(s, 3H)2.08(s, 3H), 1.97(s, 3H).

[0150] 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 (1.5 g, 27.4 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 (9.5 g, 18.3 mmol) in MeOH (400.0 mL) and stirring is continued at rt for 3 h. The mixture is neutralized with aq. 1N HCl and the solvent is removed under vacuum. Trituration in TBME gave (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 as a beige powder (7.22 g, >99%). LC-MS: R =0.66min, [M+1 ”+ =391.96. 1 H NMR (400MHz, CDCl3) δ:8.8(s, 1H), 7.84(m, 2H), 4.81(dd, J1=3.3Hz, J2=10.5Hz, 1H), 4.75(t, J=11.3Hz, 1H), 4.46(d, J=9.3Hz , 1H), 4.09(m, 1H), 3.93(dd, J1=2.5Hz, J2=6.3Hz, 1H), 3.723(t, J=6.3Hz, 1H), 3.52(m, 1H), 2.17(s, 3H).

[0151] 4. 1-((2R,3R,4S,5R,6S)-3,5-bis((4-chlorobenzyl)oxy)-2-(((4-chlorobenzyl)oxy)methyl)-6-(methylthio)tetrahydro-2H-pyran-4-yl)-4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole To a cooled (0° C.) 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 (1.0 g, 2.6 mmol) in DMF (20.0 mL), NaH (55% dispersion in oil, 0.39 g, 8.9 mmol, 3.5 eq) is added and the mixture is stirred at 0° C. for 30 min. 4-Chlorobenzyl bromide (1.9 g, 8.9 mmol, 3.5 eq) is added, the cooling bath is removed and the reaction mixture is stirred at rt for 17 h. The mixture is diluted with EA and extracted with aq.sat NH4Cl. The organic layer is washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue is purified by preparative HPLC / MS (I) to recover the title compound as a white powder (1.8 g, 92%). LC-MS: R =1.3min, [M+1 ”+ =764.12.

[0152] 5. 1-((3R,4S,5R,6R)-2-bromo-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl) tetrahydro-2H-pyran-4-yl)-4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole (Intermediate 4) NBS (0.67 g, 3.76 mmol, 2.0 eq) is added to a solution of 1-((2R,3R,4S,5R,6S)-3,5-bis((4-chlorobenzyl)oxy)-2-(((4-chlorobenzyl)oxy)methyl)-6-(methylthio)tetrahydro-2H-pyran-4-yl)-4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole (2.0 g, 1.88 mmol) in THF (130.0 mL). The reaction mixture is stirred at rt for 4 h, then quenched with water and extracted with EA (2x). The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to recover the crude intermediate 4 as a yellow oil (1.7 g, >99%), which is used without further purification. LC-MS:t R =1.30min, [M+1 ”+=797.61.

[0153] Intermediate 5 1-((2R,3R,4S,5R)-3,5-bis(benzyloxy)-2-((benzyloxy)methyl)-6-bromotetrahydro-2H-pyran-4-yl)-4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole Intermediate 5 is synthesized from intermediate 1 and benzyl bromide as a protecting group according to the procedure described for intermediate 4. LC-MS: R =1.26min, [M+1 ”+ =694.09.

[0154] Intermediate 6 N-isobutyl-2-mercapto-N-methylacetamide 1. S-(2-(isobutyl(methyl)amino)-2-oxoethyl) ethanethioate N-Methylisobutylamine (0.28 mL, 2.32 mmol, 1.2 eq), 4-DMAP (0.025 g, 0.2 mmol, 0.1 eq), TEA (1.4 mL, 10 mmol, 5.0 eq) and T3P (50% in DCM, 6.0 mL, 1.5 eq) are added to a cooled (0° C.) solution of 2-(acetylthio)acetic acid (95%, 0.3 g, 2.0 mmol) in DCM (20.0 mL). The reaction mixture is stirred at rt for 30 min and diluted with aq. 1N Partition between NaOH and EA and separate the layers. The aqueous layer is extracted with EA, the organic layers are combined, dried over Na2SO4, filtered and the solvent is removed in vacuo. The residue is purified by preparative HPLC / MS (I). S-(2-(isobutyl(methyl)amino)-2-oxoethyl) ethanethioate is extracted from the collected fractions with EA, dried over Na2SO4, filtered and the solvent is concentrated in vacuo to give the title compound (0.40 g, 98%) as a colorless oil. LC-MS (A):t R =0.71min;[M+H] + :204.09. 1 H NMR (400MHz, CDCl3) δ:8.05(s, 1H), 3.87(d, J=5.5Hz, 2H), 3.22(dd, J1=7.5Hz, J2=16.5Hz, 2H), 3.09(s, 1.5H), 2. 97(s, 1.5H), 2.40(d, J=2.8Hz, 2H), 1.94-2.07(m, 1H), 0.98(d, J=6.8Hz, 3H), 0.91(d, J=6.8Hz 3H).

[0155] 2. N-isobutyl-2-mercapto-N-methylacetamide (Intermediate 6) Aq. 1N NaOH (1.48 mL, 1.5 eq) is added to a cooled (0° C.) solution of S-(2-(isobutyl(methyl)amino)-2-oxoethyl) ethanethioate (0.20 g, 1.0 mmol, 1.0 eq) in MeOH (8.0 mL). The reaction mixture is stirred at rt for 10 min, then quenched with aq. 1N HCl and the solvent is removed under vacuum. The residue is extracted with EA, the phases are separated, the organic phase is dried over Na2SO4, filtered and the solvent is removed under vacuum to recover the crude N-isobutyl-2-mercapto-N-methylacetamide as a colorless oil (0.10 g, 63%) which is used without further purification. LC-MS (A):t R =0.66min;[M+H] + :162.2.

[0156] Intermediate 7 Intermediate 7 is prepared by adapting procedures from the literature (Ref: Chem Lett 1977, 471-474 and references cited therein).

[0157] tert-Butyl 3-hydroxy-2-mercapto-3-methylbutanoate ( Intermediate 7) To a cooled (-78°C) solution of tert-butyl 2-sulfanylacetate (1.5 g, 10.0 mmol) and TMEDA (3.4 mL, 22.3 mmol, 2.2 eq) in THF (50.0 mL) is added LDA (2.0 M in THF / Hept / ethylbenzene, 11.2 mL, 2.2 eq) dropwise. The solution is stirred at -78°C for 30 min. Then acetone (0.9 mL, 12.1 mmol, 1.2 eq) is added and stirring is continued at -78 °C for 30 min. The reaction mixture is quenched with aq.sat.NH4Cl at -78 °C, warmed to rt and diluted with EA. The two phases are separated, the organic phase is dried over Na2SO4, filtered and the solvent is concentrated under vacuum to recover the crude tert-butyl 3-hydroxy-2-mercapto-3-methylbutanoate as a yellow oil (2.5 g, >99%) which is used without further purification. LC-MS (A): R =0.78min;[M+H] + :207.09.

[0158] Intermediate 8 tert-Butyl 2-(4-hydroxy-1-methylpiperidin-4-yl)-2-mercaptoacetate (Intermediate 8) Intermediate 8 is synthesized from tert-butyl 2-sulfanylacetate and 1-methylpiperidin-4-one according to the procedure described for the synthesis of intermediate 7. LC-MS (A) t R =0.52min, [M+1 ”+ =262.10.

[0159] Intermediate 9 tert-Butyl 2-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-mercaptoacetate (Intermediate 9) Intermediate 9 is synthesized from tert-butyl 2-sulfanylacetate and tetrahydro-4H-pyran-4-one according to the procedure described for the synthesis of intermediate 7. LC-MS (A) t R =0.75min, [M+1 ”+ =249.03.

[0160] Intermediate 10 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxypiperidin-4-yl)-2-oxoethyl)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 hydrochloride (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 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.

[0161] 2. 1,1,1-trichloro-2-methylpropan-2-yl 4-(2-(tert-butoxy)-1-mercapto-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate To a cooled (-78°C) solution of tert-butyl 2-sulfanylacetate (0.12 g, 0.81 mmol) and TMEDA (0.27 mL, 0.81 mmol, 2.2 eq) in THF (10.0 mL) is added dropwise a solution of LDA (1.0 M in THF / heptane / ethylbenzene, 1.78 mL, 2.2 eq). The solution is stirred at -78°C for 10 min. 1,1,1-trichloro-2-methylpropan-2-yl 4-oxopiperidine Lysine-1-carboxylate (0.27 g, 1.38 mmol, 1.2 eq) is added at -78 °C. After 15 min, the reaction mixture is quenched with aq.sat. NH4Cl at -78 °C, then warmed to rt, diluted with EA and the phases separated. The organic phase is dried over Na2SO4, filtered and the solvent removed in vacuo to recover the crude product as a brown oil (0.456 g, >99%) without further purification. LC-MS (A):t R =1.11min;[M+H] + :449.84.

[0162] 3. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(tert-butoxy)-1-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)-2-oxoethyl)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 (1.3 g, 0.50 mmol) and 1,1,1-trichloro-2-methylpropan-2-yl 4-(2-(tert-butoxy)-1-mercapto-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate (0.152 g, 0.50 mmol, 1.0 eq) in EA (12.5 mL) is added TBAB (0.04 g, 0.25 eq). Then aq. 1M Na2CO3 (6.0 mL) is added until the reaction mixture becomes a clear solution, which is stirred at rt for 17 h. The reaction mixture is diluted with EA (10.0 mL), then with water (10.0 mL) and brine (10.0 mL). The phases are separated and the aqueous layer is extracted with EA (30.0 mL). The combined organic phases are dried over Na2SO4, filtered and the solvent is removed in vacuum. The residue is purified by preparative HPLC / MS (I) to recover the title compound (0.23 g, 54%) as a beige solid. LC-MS (A): R = 1.20 min; [M+H] + :919.23.

[0163] 4. 2-(((2S,3R,4S,5R,6R)-3,5-diacetoxy-6-(acetoxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)acetic acid To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(tert-butoxy)-1-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (2.32 g, 2.52 mmol) in DCM (13.0 mL) is added TFA (3.25 mL, 42.4 mmol, 17.0 eq) at rt. The reaction mixture is stirred at rt. After 2 h, TFA (0.33 mL, 4.24 mmol, 1.7 eq) is added and the mixture is stirred for 72 h. The mixture is carefully neutralized with aq. 1 M NaOH, diluted with DCM and the layers are separated. The aqueous layer is extracted with DCM (3x) and the organic layers are combined, dried over Na2SO4, filtered and the solvent removed in vacuo to recover the title compound (2.25 g, >99%) as a beige powder without further purification. LC-MS (A):t R =1.07min;[M+H] + :862.82.

[0164] 5. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a cooled (0° C.) solution of 2-(((2S,3R,4S,5R,6R)-3,5-diacetoxy-6-(acetoxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)acetic acid (1.0 g, 1.16 mmol) in DMF (20.0 mL) is added N-ethylmethylamine (0.2 mL, 2.31 mmol, 2.0 eq) and HATU (0.48 g, 1.22 mmol, 1.05 eq). The reaction mixture is stirred at rt for 2 h, 4 drops of DIPEA are added and stirring is continued for 35 min. The reaction mixture is partitioned between aq. 1N NaOH and DCM, the layers are separated and the aqueous layer is extracted with DCM. The organic layers are combined, dried over Na2SO4, filtered and the solvent is removed under vacuum. The residue is purified by preparative HPLC / MS (II) to recover the title compound as a colorless oil (0.60 g, 57%). LC-MS (A):t R = 1.16 min; [M+H] + :904.12.

[0165] 6. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxypiperidin-4-yl)-2-oxoethyl)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 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.56 g, 0.6 mmol) in THF (45.0 mL) and glacial acetic acid (0.84 mL) is added zinc dust (0.40 g, 6.15 mmol, 10.0 eq). The reaction mixture is stirred at rt for 1.5 h, filtered, diluted with EA then water and the layers are separated. The aqueous layer is extracted with EA, the combined organic layers are washed with brine, dried over Na2SO4, filtered and the solvent is removed in vacuo to recover a beige solid. The crude is purified by preparative HPLC / MS (I) to give the title compound as a beige powder (0.32 g, 74%). LC-MS (A): R =0.78min;[M+H] + :702.19.

[0166] Intermediate 10I ((2R,3R,4S,5R,6S)-3-acetoxy-6-((2-(ethyl(methyl)amino)-1-(4-hydroxypiperidin-4-yl)-2-oxoethyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate The title compound is prepared analogously to intermediate 10, using intermediate 14 in step 3. Intermediate 10I is obtained as a solid (0.317 g). LC-MS (A) t R =0.80min, [M+H] + =736.47.

[0167] Intermediate 10AR (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((R)-2-(ethyl(methyl)amino)-1-(3-hydroxyazetidin-3-yl)-2-oxoethyl)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 3-(2-(ethyl(methyl)amino)-1-mercapto-2-oxoethyl)-3-hydroxyazetidine- 1-Carboxylate The title compound is prepared from N-ethyl-N-methyl-2-((tetrahydro-2H-pyran-2-yl)thio)acetamide and 1,1,1-trichloro-2-methylpropan-2-yl 3-oxoazetidine-1-carboxylate as intermediate 12, as a beige solid (0.11 g). LC-MS (A) t R =0.93min, [M+H] + =405.05.

[0168] 2. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((R)-2-(ethyl(methyl)amino)-1-(3-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)azetidin-3-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate The title compound is prepared from 1,1,1-trichloro-2-methylpropan-2-yl 3-(2-(ethyl(methyl)amino)-1-mercapto-2-oxoethyl)-3-hydroxyazetidine-1-carboxylate and intermediate 3 analogously to intermediate 10, step 3. Purification of the crude by preparative HPLC / MS (I) allowed the R-epimer to be isolated as a beige solid (0.027 g). LC-MS (A) t R =1.09min, [M+H] + =878.23.

[0169] 3. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((R)-2-(ethyl(methyl)amino)-1-(3-hydroxyazetidin-3-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (Intermediate 10AR) To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((R)-2-(ethyl(methyl)amino)-1-(3-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)azetidin-3-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.26 g, 0.03 mmol) in THF (1.7 mL) and AcOH (0.0042 mL) is added zinc dust (0.019 g, 10.0 eq). The reaction mixture is stirred at rt for 15 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 Na2SO4, filtered and the solvent is removed in vacuo to recover the title compound as a crude pale yellow solid (0.025 g) without further purification. LC-MS (A) t R =0.77min, [M+H] + =674.21.

[0170] Intermediate 10AS (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-2-(ethyl(methyl)amino)-1-(3-hydroxyazetidin-3-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Intermediate 10AS is obtained as described for intermediate 10AR. In the preparative HPLC / MS(I) purification of intermediate 10AR in step 2, the S epimer is also separated and isolated.

[0171] 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-2-(ethyl(methyl)amino)-1-(3-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)azetidin-3-yl (4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate The title compound is prepared analogously to Intermediate 10AR, step 2. as a beige solid (0.026 g). LC-MS (A) t R=1.10min, [M+H] + =878.23.

[0172] 2. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-2-(ethyl(methyl)amino)-1-(3-hydroxyazetidin-3-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate The title compound was obtained as a beige solid (crude, 0.019 g) similar to intermediate 10AR without further purification. LC-MS (A) t R =0.77min, [M+H] + =674.12.

[0173] Intermediate 11 N-Cyclobutyl-2-(1-hydroxycyclohexyl)-2-mercapto-N-methylacetamide 1. S-(2-(cyclobutyl(methyl)amino)-2-oxoethyl) ethanethioate To a solution of 2-(acetylthio)acetic acid 95% (1.0 g, 6.71 mmol) in DMF (8.0 mL) is added HATU (2.8 g, 7.04 mmol, 1.05 eq) and the mixture is cooled to 0° C. Cyclobutyl-methyl-amine (0.65 g, 7.38 mmol, 1.1 eq) and DIPEA (1.29 mL, 7.38 mmol, 1.7 eq) in DMF (2.0 mL) are added and the mixture is stirred at rt for 15 h. The reaction mixture is concentrated to half of the original volume, filtered and purified by prep HPLC (II) to recover the title product (1.05 g, 78%) as a pale yellow oil. LC-MS (A) t R =0.68min, [M+H] + =202.15.

[0174] 2. N-Cyclobutyl-2-mercapto-N-methylacetamide To a solution of S-(2-(cyclobutyl(methyl)amino)-2-oxoethyl) ethanethioate (1.05 g, 5.22 mmol) in MeOH (10.0 mL) is added NH4Cl (0.87 mL) and stirring is continued at rt for 4 h. The reaction mixture is acidified with aq 1N HCl, the solvent is removed in vacuo and extracted with EA (2x). The organic layers are combined, dried over Na2SO4, filtered and concentrated in vacuo to recover the title compound as a light purple oil (0.905 g, >99%). LC-MS (A) t R =0.61min, [M+H] + =160.18.

[0175] 3. N-Cyclobutyl-2-(1-hydroxycyclohexyl)-2-mercapto-N-methylacetamide A spatula tip of molecular sieves (4 Å) is added to a solution of N-cyclobutyl-2-mercapto-N-methylacetamide (0.831 g, 5.22 mmol) in THF (25.0 mL). The solution is cooled to -78 °C and TMEDA (1.74 mL, 11.5 mmol, 2.2 eq) is added, followed by dropwise addition of LDA (1.0 M in THF / heptane / ethylbenzene, 11.5 mL, 2.2 eq). The solution is stirred at -78 °C for 20 min, then cyclohexanone (0.65 mL, 1.2 eq) is added and after 30 min the reaction mixture is quenched with aq.sat. NH4Cl at -78 °C. The mixture is warmed to rt and EA is added. The two phases are separated and the organic phase is dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified by prep HPLC (II) to give the desired product as a colorless oil ( 0.420 g, 31%). LC-MS(A) t R =0.89min, [M+H] + =257.93.

[0176] Intermediate 12 N-Ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-mercapto-N-methylacetamide 1. Ethyl 2-((tetrahydro-2H-pyran-2-yl)thio)acetate 3,4-Dihydro-2H-pyran (1.1 mL, 11.5 mmol) is slowly added to a cooled (0° C.) mixture of ethyl thioglycolate (1.3 mL, 11.5 mmol, 1.0 eq) in HCl 37% (0.5 mL). The reaction mixture is stirred at 0° C. for 2 h and then quenched with Et2O. The organic layer is washed with aq. 10% NaHCO3, dried over Na2SO4, filtered and the solvent is removed under vacuum to give the crude. Purification by Flash Master (ISCO, product bound onto isolute, 24 g column, Hept / EA 100 / 0 to 0 / 100) afforded the title product as a beige oil (1.94 g, 82%). LC-MS (A):t R =0.79min;[M+H] + :205.17.

[0177] 2. 2-((tetrahydro-2H-pyran-2-yl)thio)acetic acid To a cooled (0° C.) solution of ethyl 2-((tetrahydro-2H-pyran-2-yl)thio)acetate (1.8 g, 6.8 mmol) in EtOH (40.0 mL) is added aq. 2N NaOH (8.5 mL, 17.0 mmol, 2.5 eq). The reaction mixture is stirred at 0° C. for 30 min, acidified with aq. 2N HCl, concentrated in vacuo, then partitioned between EA and water. The organic layer is washed with water, dried over Na2SO4, filtered, and the solvent is removed in vacuo to give the crude product, which is purified by preparative HPLC / MS (II) to give the title compound as a colorless oil (1.01 g, 80%). LC-MS (A):t R =0.54min;[M+H] + :177.22.

[0178] 3. N-Ethyl-N-methyl-2-((tetrahydro-2H-pyran-2-yl)thio)acetamide To a solution of 2-((tetrahydro-2H-pyran-2-yl)thio)acetic acid (0.50 g, 2.84 mmol, 1.0 eq) in DMF (8.0 mL) is added HATU (1.20 g, 2.98 mmol, 1.05 eq) and the mixture is cooled to 0° C. A solution of N-ethylmethylamine 97% (0.3 mL, 3.4 mmol, 1.2 eq) and DIPEA (0.6 mL, 3.12 mmol, 1.7 eq) in DMF (1.0 mL) is added and the mixture is stirred at rt for 15 h. The reaction mixture is directly purified by preparative HPLC / MS (I) to give the title compound as a beige oil (0.56 g, 92%). LC-MS (A):t R =0.67min;[M+H] + :218.24.

[0179] 4. N-Ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-2-((tetrahydro-2H-pyran-2-yl)thio)acetamide To a cooled (-78°C) solution of N-ethyl-N-methyl-2-((tetrahydro-2H-pyran-2-yl)thio)acetamide (0.27 g, 1.24 mmol) in THF (12.0 mL) was added molecular sieves (4 Å) and TMEDA (0.41 mL, 2.73 mmol, 2.2 eq), followed by dropwise addition of LDA solution (1.0 M in THF / Hept / ethylbenzene, 2.73 mL, 2.73 mmol, 2.2 eq) while keeping the solution below -70°C. The solution was stirred at -78°C for 20 min, then tetrahydro-4H-pyran-4-one (0.14 mL, 1.49 mmol, 1.2 eq) was added and stirring was continued at -78°C for 1 h. The reaction mixture is quenched with aq.sat.NH4Cl at -78 °C, warmed to rt, diluted with EA, the phases separated and the aqueous phase extracted with EA (3x). The organic layers are combined, dried over Na2SO4, filtered and the solvent removed in vacuo to give an oil. It is purified by preparative HPLC / MS (II) to give the title compound as a yellow oil (0.27 g, 67%). LC-MS (A): R =0.69min;[M+H] + :318.18.

[0180] 5. N-Ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-mercapto-N-methylacetamide (Intermediate 12) To a solution of N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-2-((tetrahydro-2H-pyran-2-yl)thio)acetamide (0.27 mg, 0.83 mmol, 1.0 eq) in THF (8.0 mL) is added AgNO3 (0.29 g, 1.69 mmol, 2.0 eq) and water (8.0 mL). The reaction mixture is stirred for 20 min, then diluted with DCM (45.0 mL), NaSH (466.0 mg, 8.32 mmol, 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 layers of the filtrate are separated and the organic layer is washed with aq.sat.NH4Cl, dried over Na2SO4, filtered and the solvent removed in vacuo to give an oil which is purified by preparative HPLC / MS (II) to give the title product as a yellow solid (0.14 g, 73%). LC-MS (A): R =0.56min;[M+H] + :234.18. 1 H NMR (400MHz, CDCl3) δ:3.82-3.74(m, 4H), 3.50-3.39(m, 1.5H), 3.33-3.18(m, 1.5H), 3.05(s, 1.5H), 2.93(s, 1.5H), 2.38-2.17(m, 1H), 2.13-2. 02(bd, J=13.5Hz, 1H), 1.70-1.46(m, 2H), 1.42-1.32(m, 1H), 1.26-1.19(bt, J=6.5Hz, 1.5H), 1.17-1.1(bt, J=7.0Hz, 1.5H).

[0181] Intermediate 13 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-((2-(ethyl(methyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate (Intermediate 13) To a solution of intermediate 12 (0.14 g, 0.61 mmol, 1.0 eq) in aq. 10% Na2CO3 (6.0 mL) is added TBAHS (1.30 g, 3.65 mmol, 6.0 eq). To this mixture is added intermediate 2 (0.29 g, 1.03 mmol, 1.2 eq) in EA (12.0 mL) and the mixture is stirred at rt for 48 h and diluted with EA, water and brine. The phases are separated and the aqueous layer is extracted with EA (3x). The combined organic phases are dried over Na2SO4, filtered and the solvent is removed under vacuum. The resulting product is purified by preparative HPLC / MS (I) to give the title compound as a beige powder (0.20 g, 61%). LC-MS (A):t R =0.81min;[M+H] + :547.2.

[0182] Intermediate 14 ((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 Intermediate 14 is prepared from (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 Intermediate 4, step 3.

[0183] 1. (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 intermediate 4 step 3. (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 is removed in vacuo to give the crude which is purified by Flash Master (ISCO, product added to 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.

[0184] 2. 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 AgO (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 added to 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.

[0185] 3. (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 (6.18 g, 13.9 mmol) in THF (200.0 mL) is added a mixture of (AcOH / water 1 / 1, 600.0 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 layer is extracted with EA (2x). The organic layers are combined, dried over Na2SO4, filtered and the solvent is removed under vacuum to recover the title compound as a beige solid (29.00 g, >99%) which is used without further purification. LC-MS (A):t R =0.80min;[M+H] + :405.96.

[0186] 4. ((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) 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 was partitioned between EA and water, the phases were separated, and the organic layer The residue is washed with water, dried over Na2SO4, filtered and the solvent removed in vacuo to give a beige solid. Purification on Flash master (ISCO, product loaded onto isolute, 120 g column, Hept / EA 95 / 5 to 30 / 70) afforded the title compound as a white solid (5.66 g, 83%). LC-MS (A): R =1.00min;[M+H] +:490.07.

[0187] 5. ((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 14) NBS (4.00 g, 22.4 mmol, 2.0 eq) is added to a solution of ((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 (5.66 g, 11.2 mmol) in DCM (165.0 mL). The reaction mixture is stirred at rt for 15 h, quenched with water and diluted with DCM. The layers are separated and the aqueous layer is extracted with DCM (2x). The combined organic layers are washed with brine, dried over Na2SO4, filtered and the solvent is removed in vacuo to give the crude product. Purification by Flash Master (ISCO, product loaded onto isolute, 80 g column, Hept / EA 100 / 0 to 30 / 70) afforded the title compound as a beige solid (1.72 g, 29%). LC-MS (A): 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).

[0188] Intermediate 15 ((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 15 is prepared from intermediate 1 according to the procedure described for intermediate 14. In step 5, EtI is added to the reaction mixture. Intermediate 15 is obtained as a white powder. LC-MS (A): R =1.03min;[M+H] + :538.15.

[0189] Preparation of the Reference Example Reference Example 1 Example 2.53.203. 2-(((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)-N-ethyl-N,3-dimethylbutanamide 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((1-(tert-butoxy)-3-methyl-1-oxobutan-2-yl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate TBAB (0.073 g, 0.23 mmol, 0.25 eq) was mixed with intermediate 3 (0.50 g, 0.9 mmol) and tert-butyl 3-methyl-2-sulfanylbutanoate (0.24 g, 1.27 mmol, 1.4 eq) is added to a solution of 1.0 g of 1M Na2CO3 in 10.0 mL. Then aq. 1M Na2CO3 is added (2.0 mL) and the mixture is stirred at rt for 17 h. TBAB (1 spatula tip), tert-butyl 3-methyl-2-sulfanylbutanoate (5 drops) and aq. 1M Na2CO3 (1.0 mL) are added again. After stirring at rt for 4 h, the reaction mixture is diluted with EA (25.0 mL), then with water (25.0 mL) and with brine (25.0 mL). The phases are separated and the aqueous layer is extracted with EA (50.0 mL). The combined organic phases are dried over Na2SO4, filtered and the solvent is removed under vacuum. The residue is purified by preparative HPLC / MS (I) to recover the title compound (0.2 g, 32%) as a beige solid which is used without further purification. LC-MS(A):t R = 1.16 min; [M+H] + :660.31.

[0190] 2. 2-(((2S,3R,4S,5R,6R)-3,5-diacetoxy-6-(acetoxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-methylbutanoic acid To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((1-(tert-butoxy)-3-methyl-1-oxobutan-2-yl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.2 g, 0.3 mmol) in DCM (45.0 mL) is added TFA (0.38 mL, 5.0 mmol, 17 eq) at rt. The reaction mixture is stirred at rt for 72 h, then neutralized with aq. 1N NaOH, diluted with DCM and the layers are separated. The aqueous layer is extracted with DCM (3x). The organic layers are combined, dried over Na2SO4, filtered and the solvent removed in vacuo to recover the title compound (0.17 g, 96%) as a beige powder without further purification. LC-MS (A): R =0.98min;[M+H] + :604.28.

[0191] 3. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((1-(ethyl(methyl)amino)-3-methyl-1-oxobutan-2-yl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate A solution of HATU (0.035 g, 0.087 mmol, 1.05 eq) followed by N-ethylmethylamine (97%, 0.015 mL, 0.17 mmol, 2.0 eq) and DIPEA (0.032 mL, 0.182 mmol, 2.2 eq) in DMF (2.0 mL) is added to a cooled (0° C.) solution of 2-(((2S,3R,4S,5R,6R)-3,5-diacetoxy-6-(acetoxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-methylbutanoic acid (0.05 g, 0.08 mmol) in DMF (2.0 mL). The reaction mixture is stirred at rt for 1.5 h, then it is partitioned between aq. 1N NaOH and DCM. The layers are separated, the aqueous layer is extracted with DCM, the organic layers are combined, dried over Na2SO4, filtered and the solvent is removed under vacuum. The residue is purified by preparative HPLC / MS (I) to recover the title compound as a beige solid (0.044 g, 82%). LC-MS (A):t R =1.03min;[M+H] + :645.15.

[0192] 4. 2-(((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)-N-ethyl-N,3-dimethylbutanamide (Reference Example 1) K2CO3 (0.002 g, 0.012 mmol, 0.2 eq) was added to (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((1-(ethyl(methyl)amino)-3-methyl-1-oxobutan-2-yl)thio)-4-(4-(3,4, Add 5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.042 g, 0.06 mmol) to a solution in MeOH (20.0 mL). Stir the reaction mixture at rt for 2 h, quench with MeCN and then water, and purify the mixture directly by preparative HPLC / MS (I) to recover the title compound as a beige solid (0.032 g, 94%). LC-MS (A):t R =0.085min;[M+H] + :545.32.

[0193] Reference Example 2 Example 2.56.203S. (S)-2-(((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)-N-ethyl-N-methyl-2-(tetrahydro-2H-pyran-4-yl)acetamide 1. Methyl 2-bromo-2-(tetrahydro-2H-pyran-4-yl)acetate Methyl 2-(tetrahydro-2H-pyran-4-yl)acetate (5.0 g, 31.6 mmol) is dissolved in THF (60.0 mL) and cooled to -75 °C. NaHMDS (1 M in THF, 35.0 mL, 35.0 mmol, 1.1 eq) is added dropwise and the reaction mixture is stirred at -75 °C for 30 min. TMSCl (4.0 mL, 31.6 mmol, 1.0 eq) is added dropwise and stirring is continued at -75 °C for 1 h. NBS (5.62 g, 31.6 mmol, 1.0 eq) is added, the cooling bath is removed and the mixture is stirred at rt for 1 h. It is then diluted with EA, the layers are separated, the organic layer is washed with water, dried over Na2SO4, filtered and the solvent is removed under reduced pressure. The residue is purified by CC on silica gel eluting with (Hept: / EA 3 / 1) to give methyl 2-bromo-2-(tetrahydro-2H-pyran-4-yl)acetate (5.8 g, 78%). 1 H NMR (400MHz, CDCl3) δ:4.03(d, J=9.3Hz, 1H), 4.00(m, 2H), 3.81(s, 3H), 3.42(m, 2H), 2.15(m, 1H), 1.99(m, 1H), 1.64(m, 1H), 1.41(m, 2H).

[0194] 2. Methyl 2-(acetylthio)-2-(tetrahydro-2H-pyran-4-yl)acetate To a solution of methyl 2-bromo-2-(tetrahydro-2H-pyran-4-yl)acetate (5.8 g, 24.5 mmol) in acetone (80.0 mL) is added potassium acetate (3.36 g, 29.5 mmol, 1.2 eq) at rt and stirring is continued at rt for 1 h. The reaction mixture is filtered and the filtrate is diluted with EA and washed with brine. The layers are separated and the organic layer is washed with water, dried over Na2SO4, filtered and the solvent is removed under reduced pressure to give the title compound without further purification. LC-MS (C):t R =0.74min;[M+H] + :233.19.

[0195] 3. Methyl 2-mercapto-2-(tetrahydro-2H-pyran-4-yl)acetate Sodium metal (0.20 g, 8.6 mmol) is dissolved in MeOH (100.0 mL), methyl 2-(acetylthio)-2-(tetrahydro-2H-pyran-4-yl)acetate (5.4 g, 23.2 mmol) is added and the reaction mixture is stirred at rt for 4 h. The reaction mixture is quenched with aq 10% citric acid, the layers are separated and the aqueous layer is extracted with DCM (3x). The organic layer is washed with water, dried over Na2SO4, filtered and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC / MS to give methyl 2-mercapto-2-(tetrahydro-2H-pyran-4-yl)acetate (1.6 g, 36%). LC-MS (C):t R =0.70min;[M+H] + :191.36.

[0196] 4. Methyl 2-(((2S,3R,4S,5R,6R)-3,5-bis(benzyl) oxy)-6-((benzyloxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(tetrahydro-2H-pyran-4-yl)acetate To a solution of intermediate 5 (3.05 g, 2.95 mmol) and methyl 2-mercapto-2-(tetrahydro-2H-pyran-4-yl)acetate (0.84 g, 4.43 mmol, 1.5 eq) in EA (65.0 mL) is added TBAB (0.24 g, 0.74 mmol, 0.25 eq) followed by aq. 1M Na2CO3 (15.0 mL) and the reaction mixture is stirred at rt for 30 min. 2-mercapto-2-(tetrahydro-2H-pyran-4-yl)acetate (0.56 g, 3.0 mmol, 1.0 eq) is added again and stirring is continued at rt for 1 h. The reaction mixture is diluted with water (25.0 mL), the layers are separated and the aqueous layer is extracted with EA (2x). The combined organic phases are dried over Na2SO4, filtered and concentrated in vacuo to recover the crude product which is purified by CC on silica gel eluting with EA / Hept 50 / 50 to give the title compound (1.3 g, 55%). LC-MS (C):t R =1.36min;[M+H] + :804.47.

[0197] 5. 2-(((2S,3R,4S,5R,6R)-3,5-bis(benzyloxy)-6-((benzyloxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(tetrahydro-2H-pyran-4-yl)acetic acid To a solution of methyl 2-(((2S,3R,4S,5R,6R)-3,5-bis(benzyloxy)-6-((benzyloxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(tetrahydro-2H-pyran-4-yl)acetate (1.3 g, 1.62 mmol) in THF (25.0 mL) and EtOH (15.0 mL) is added aq. 1M NaOH (15.0 mL) and it is stirred at rt for 1.5 h. The reaction mixture is quenched with aq. 1M HCl (pH=5), the layers are separated and the aqueous layer is extracted with EA (2x). The combined organic phases are dried over Na2SO4, filtered and concentrated in vacuo to recover the crude product which is purified by preparative HPLC / MS to give the title compound (0.65 g, 51%). LC-MS(C):t R =1.29min;[M+H] + :790.21.

[0198] 6. 2-(((2S,3R,4S,5R,6R)-3,5-bis(benzyloxy)-6-((benzyloxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-N-methyl-2-(tetrahydro-2H-pyran-4-yl)acetamide 2-(((2S,3R,4S,5R,6R)-3,5-bis(benzyloxy)-6-((benzyloxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(tetrahydro-2H-pyran-4-yl)acetic acid (0.63 g, 0.8 mmol) is dissolved in DMF (15.0 mL) and the solution is cooled to 0° C. DIPEA (0.27 mL, 0.755 mmol, 2.0 eq) is added, followed by ethylmethylamine (0.14 mL, 1.6 mmol, 2.0 eq) and then HATU (0.33 g, 0.84 mmol, 1.0 eq) and stirring is continued at rt for 1 h. The reaction mixture is diluted with water, a spatula of NaCl is added, the layers are separated and the aqueous layer is extracted with EA (2x). The combined organic phases are dried over Na2SO4, filtered and concentrated in vacuo to recover the crude product which is purified by CC on silica gel eluting with EA / Hept 50 / 50 to 100 / 0 to give the title compound (0.6 g, 91%). LC-MS (C):t R =1.33min;[M+H] + :831.52.

[0199] 7. 2-(((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)-N-ethyl-N-methyl-2-(tetrahydro-2H-pyran-4-yl)acetamide To a cooled (0° C.) solution of 2-(((2S,3R,4S,5R,6R)-3,5-bis(benzyloxy)-6-((benzyloxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-N-methyl-2-(tetrahydro-2H-pyran-4-yl)acetamide (0.55 g, 0.66 mmol) in DCM (20.0 mL) is added BBr3 (1 M in DCM, 4.0 mL). The reaction mixture is stirred at 0° C. for 10 min and then quenched by the addition of ice-water. The layers are separated and the aqueous layer is extracted with DCM (2×). The combined organic phases are dried over Na2SO4, filtered and concentrated in vacuo to recover the crude product, which is purified by preparative HPLC / MS (I) to give the title compound (0.035 g, 9%). LC-MS (C): R =0.72min;[M+H] + :562.21.

[0200] 8. (S)-2-(((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)-N-ethyl-N-methyl-2-(tetrahydro-2H-pyran-4-yl)acetamide (Reference Example 2).

[0201] Separation of the epimers of Example 2.56.203S. (0.035 g) by chiral preparative HPLC (I) afforded the title compound (0.004 g). LC-MS (C): R =0.72min;[M+H] + : 562.21. Chiral analytical HPLC (E): t R =2.36min.

[0202] The LC-MS and Gal-3 inhibition data from Reference Examples 1 and 2 are set forth in Table 1 below. The LC-MS conditions used were LC-MS(A) for Reference Example 1 and LC-(MS(C) for Reference Example 2.

[0203] [Table 6] Preparation of Compounds of Structure 1 and Examples Thereof Example 2.41.200. 2-(((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-(4-hydro (2H-pyran-4-yl)-N-isobutyl-N-methylacetamide 1. 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-N-isobutyl-N-methylacetamide Intermediate 4 (0.60 g, 0.44 mmol) and N-isobutyl-2-mercapto-N-methylacetamide (Intermediate 6) (0.10 g, 0.44 mmol, 1.0 eq) are dissolved in EA (12.5 mL). TBAB (0.036 g, 0.11 mmol, 0.25 eq) in aq. 1M Na2CO3 (6.25 mL) is added and stirring is continued for 17 h. The reaction mixture is diluted with EA (25.0 mL), water (25.0 mL) and brine (25.0 mL), the phases are separated and the aqueous layer is extracted with EA (50.0 mL). The organic phases are combined, dried over Na2SO4, filtered and concentrated under vacuum. The material is purified by preparative HPLC / MS (I) to recover the title compound (0.064 g, 16%) as a beige solid. LC-MS (A):t R =1.30min;[M+H] + :877.23.

[0204] 2. 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide To a cooled (-78°C) solution of 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-N-isobutyl-N-methylacetamide (0.03 g, 0.03 mmol) and TMEDA (0.01 mL, 0.07 mmol, 2.2 eq) in THF (1.8 mL) is added dropwise LDA (1.0 M in THF / Hept / ethylbenzene, 0.07 mL, 0.07 mmol, 2.2 eq). The solution is stirred at -78 °C for 1 h and tetrahydro-4H-pyran-4-one (0.004 mL, 0.004 mmol, 1.2 eq) is added at -78 °C. After 1 h, the reaction mixture is quenched with aq.sat. NH4Cl at -78 °C, warmed to rt and diluted with EA and toluene. The phases are separated, the organic phase is dried over Na2SO4, filtered and the solvent is removed under vacuum. The crude is purified by preparative HPLC / MS (I) to recover the title compound (0.022 g, 75%) as a beige solid. LC-MS (A): t R =1.31min;[M+H] + :979.31.

[0205] 3. 2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide (2.41.200.) To a cooled (0° C.) solution of 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide (0.022 g, 0.023 mmol) in DCM (5.0 mL) is added BBr3 (1 M in DCM, 0.14 mL, 6.0 eq). The reaction mixture is stirred at 0° C. for 2 h and quenched by dropwise addition of water at 0° C. The mixture is extracted with DCM (2x), the layers are separated, and the organic layers are combined, washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material is purified by preparative HPLC / MS (I) to recover the title compound (0.003 g, 24%) as a beige powder. LC-MS (A): R =0.79min;[M+H] + :605.49.

[0206] Example 2.41.200R. (R)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide (2.41.200R.) Separation of the epimers of Example 2.41.200. (0.022 g) by chiral preparative HPLC (II) afforded the title compound (0.013 g) as a beige solid. R =1.44min;[M+H] + :605.41. 1 H NMR (400MHz, MeOD) δ:8.6,(s, 1H), 7.65(m, 2H), 4.9-4.82(m, 2H), 4.24-4.13(m, 3H), 3.91-3.83(m, 1H), 3.82-3.73(m, 6H), 3.35-3.18 (m, 2H), 3.29(s, 2.5H), 2.97(s, 0.5H), 1.92-2.13(m, 2H), 1.83-1.73(m, 1H), 1.67-1.55(m, 1H), 1.6-0.92(m, 6H).

[0207] Example 2.41.200S. (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide Separation of the epimers of Example 2.41.200. (0.022 g) by chiral preparative HPLC (II) gave Example 2.41.200S. (0.013 g) as a beige solid. Chiral analytical HPLC (F): R =2.02min;[M+H] + :605.41.

[0208] The LC-MS and Gal-3 inhibition data for Example 2.41.200. are listed below in Table 2. The LC-MS conditions used were LC-MS(A). Chiral HPLC (conditions and retention times) and inhibition data for the epimers R and S of Example 2.41.200. are also listed.

[0209] [Table 7] Example 2.31.201. 2-(((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-hydroxy-N,N,3-trimethylbutanamide 1. tert-Butyl 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-hydroxy-3-methylbutanoate Intermediate 4 (1.6 g, 1.2 mmol) and tert-butyl 3-hydroxy-2-mercapto-3-methylbutanoate (Intermediate 7) (0.35 g, 1.7 mmol, 1.4 eq) are dissolved in EA (12.5 mL) and TBAB (0.89 g, 1.55 mmol, 0.25 eq) in aq. 1M Na2CO3 (6.2 mL) is added. The mixture is stirred for 17 h and diluted with EA (25.0 mL), water (25.0 mL) and brine (25.0 mL). The phases are separated and the aqueous layer is extracted with EA (50.0 mL). The combined organic phases are dried over Na2SO4, filtered and the solvent is removed under vacuum. The residue is purified by preparative HPLC / MS (II) to recover the title compound as a beige solid (0.55 g, 49%). LC-MS (A):t R =1.33min;[M+H] + :922.15.

[0210] 2. 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-hydroxy-3-methylbutanoic acid TFA (0.23 mL, 3.0 mmol, 5.0 eq) was added at rt to tert-butyl Add 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-hydroxy-3-methylbutanoate (0.55 g, 0.6 mmol) to a solution in DCM (50.0 mL) and stir at rt for 17 h. Add TFA (0.23 mL, 1.55 mmol, 5.0 eq) again and stir at rt for another 48 h. Carefully neutralize the mixture with aq. 1M NaOH, dilute with DCM and separate the layers. Extract the aqueous layer with DCM (3x). The organic layers are combined, dried over Na2SO4, filtered and the solvent removed in vacuo to recover the crude title compound as a beige solid (0.48 g, 93%) which is used without further purification. LC-MS (A): R =1.21min;[M+H] + :868.10.

[0211] 3. 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-hydroxy-N,N,3-trimethylbutanamide To a solution of crude 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-hydroxy-3-methylbutanoic acid (0.8 g, 0.09 mmol) in DMF (1.0 mL) at rt was added successively EDC HCl (0.044 mg, 0.23 mmol, 2.5 eq), HOBT (0.017 g, 0.11 mmol, 1.2 eq), 4-DMAP (0.003 g, 0.023 mmol, 0.25 eq), DIPEA (0.047 mL, 0.277 mmol, 3.0 eq) and dimethylamine (0.008 g, 0.185 mmol, 2.0 eq) are added. The reaction mixture is stirred at rt for 4 h, then dimethylamine (0.002 g, 0.0046 mmol, 0.5 eq), DIPEA (0.008 mL, 0.07 mmol, 0.5 eq), a spatula tip of HOBT, EDC HCl and 4-DMAP are added again. After a further 2 h at rt, the reaction mixture is partitioned between aq. 1N NaOH and EA, the layers are separated and the aqueous layer is extracted with EA. The combined organic layers are dried over Na2SO4, filtered and the solvent is removed under vacuum. The crude is purified by preparative HPLC / MS (I) to recover the title compound (0.018 g, 22%) as a beige solid. LC-MS (A): R = 1.25 min; [M+H] + :895.56.

[0212] 4. 2-(((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-hydroxy-N,N,3-trimethylbutanamide (2.31.201.) A cooled (0° C.) solution of 2-(((2S,3R,4S,5R,6R)-3,5-bis((4-chlorobenzyl)oxy)-6-(((4-chlorobenzyl)oxy)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-3-hydroxy-N,N,3-trimethylbutanamide (0.018 g, 0.02 mmol) in DCM (2.0 mL) was To the solution is added BBr3 solution (1M in DCM, 0.2 mL, 10.0 eq). The reaction mixture is stirred at 0° C. for 1.5 h and then quenched by dropwise addition of water at 0° C. The layers are separated, the aqueous layer is extracted with DCM (2×), the organic layers are combined, washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue is purified by preparative HPLC / MS (I) to recover the title compound as a beige powder (0.008 g, 73%). LC-MS (A):t R =0.67min;[M+H] + :521.41.

[0213] Example 2.31.203R. (R)-2-(((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)-N-ethyl-3-hydroxy-N,3-dimethylbutanamide ( 2.31.203R.) Example 2.31.203. is prepared as described for Example 2.31.201. Separation of the epimers of Example 2.31.203. (0.097 g) by chiral preparative HPLC (III) afforded the title compound (0.029 g) as a white powder. Chiral analytical HPLC (G): R =1.43min.

[0214] Example 2.31.203S. (S)-2-(((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)-N-ethyl-3-hydroxy-N,3-dimethylbutanamide Separation of the epimers of Example 2.31.203. (0.097 g) by chiral preparative HPLC (III) similar to Example 2.31.203R. afforded the title compound (0.047 g) as a white powder. Chiral analytical HPLC (G): R =2.1min.

[0215] The following examples are prepared starting from intermediate 4 or intermediate 5, and intermediate 7 following the procedure described for example 2.31.201. The LC-MS and Gal-3 inhibition data are listed in Table 3 below. The LC-MS conditions used are 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.

[0216] [Table 8]

[0217] [Table 9] The following examples are prepared starting from Intermediate 4 or Intermediate 5 and Intermediate 8 or Intermediate 9 following the procedures described for Example 2.31.201. The LC-MS and Gal-3 inhibition data are listed in Table 4 below. The LC-MS conditions used are 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.

[0218] [Table 10]

[0219] [Table 11]

[0220] [Table 12]

[0221] [Table 13]

[0222] [Table 14]

[0223] [Table 15]

[0224] [Table 16]

[0225] [Table 17]

[0226] [Table 18]

[0227] [Table 19]

[0228] [Table 20]

[0229] [Table 21]

[0230] Example 2.41.203. 2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(tert-butoxy)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H -1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl Diacetate TBAB (0.22 g, 0.681 mmol, 0.25 eq) followed by aq. 1M Na2CO3 (8.0 mL) is added to a solution of intermediate 3 (1.5 g, 2.73 mmol) and tert-butyl 2-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-mercaptoacetate (intermediate 8) (0.95 g, 1.4 eq) in EA (35.0 mL). The mixture is stirred at rt for 17 h and diluted with EA (25.0 mL), water (25.0 mL) and brine (25.0 mL). The phases are separated and the aqueous layer is extracted with EA (50.0 mL). The organic phases are combined, dried over Na2SO4, filtered and concentrated under vacuum. The residue is analyzed by Flash Master (ISCO; the compound is bound on an isolute and purified by EA / Hept 0 / 100 to 70 / 30) to recover the title compound as a beige powder (1.8 g, 91%). LC-MS (A): R =1.04-1.05min;[M+H] + :717.92.

[0231] 2. 2-(((2S,3R,4S,5R,6R)-3,5-diacetoxy-6-(acetoxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(tert-butoxy)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (3.8 g, 4.32 mmol) in DCM (80.0 mL) is added TFA (4.9 mL, 17.0 eq) at rt. The reaction mixture is stirred at rt for 17 h, carefully quenched by addition of aq. 2N NaOH (until pH=7), diluted with DCM and the layers are separated. The aqueous layer is extracted with EA (3x). The organic layers are combined, dried over Na2SO4, filtered and the solvent removed in vacuo to recover the title compound as a beige powder (3.8 g, >99%) which is used without further purification. LC-MS (A): R =0.86min;[M+H] + :662.29.

[0232] 3. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate 2-(((2S,3R,4S,5R,6R)-3,5-diacetoxy-6-(acetoxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetic acid (4.0 g, 6.0 mmol) is dissolved in DMF (40.0 mL). HATU (2.53 g, 6.32 mmol, 1.05 eq) is added followed by a solution of N-ethylmethylamine (0.8 mL, 9.03 mmol, 1.5 eq) and DIPEA (1.8 mL, 10.2 mmol, 1.7 eq) in DMF (10.0 mL). The reaction mixture is stirred at rt for 17 h and then partitioned between EA and water. The organic phase is washed with water, the combined aqueous phases are extracted with EA. The combined organic phases are dried over Na2SO4, filtered and concentrated in vacuo to recover the crude product which is purified by Flash Master (ISCO, column 80 g, compound bound on isolute and eluted with EA / Hept 35 / 65 to 100 / 0). The title compound is obtained as a beige powder (2.28 g, 54%). LC-MS (A):t R =0.96min;[M+H] + :703.16.

[0233] 4. 2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide (2.41.203.) To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.72 g, 1.02 mmol) in MeOH (10.0 mL) is added K2CO3 (0.028 g, 0.2 eq) at rt. The reaction mixture is stirred at rt, diluted with MeCN and water and purified directly by preparative HPLC / MS (I) to recover the title compound as a beige powder (0.5 g, 85%). LC-MS (A):t R =0.71min;[M+H] + :577.98.

[0234] Example 2.41.203R. (R)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide Separation of the epimers of Example 2.41.203. (2.77 g) by chiral preparative HPLC / MS (IV) afforded the title compound (0.88 g) as a white powder. Chiral analytical HPLC (H): R =1.53min;[M+H] + :605.41. 1 H NMR (400MHz, MeOD) δ:8.53(s, 0.4H), 8.51(s, 0.6H), 7.65(m, 2H), 4.87(m, 1H), 4.82(d, J1=9.5Hz , 1.0H), 4.2(t, 10.5Hz, 1H), 4.16(s, 1H), 4.4(d, J=2.5Hz, 1H), 3.95-3.71(m, 7 H), 3.55-3.4(m, 2H), 3.28(s, 1.8H), 2.7(s, 1.2H), 2.13-1.92(m, 2H), 1.83-1. 73(m, 1H), 1.62-1.55(m, 1H), 1.3(t, J=7.0Hz, 1.3H), 1.15(t, J=7.0Hz, 1.8H).

[0235] Example 2.41.203S. (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide [1,3-di-deoxy-1-((N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide)-(S)-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside] Separation of the epimers of Example 2.41.203. (2.77 g) by chiral preparative HPLC / MS (IV) afforded the title compound (0.163 g) as a white powder. R =2.4min;[M+H] + :605.41. 1 H NMR (400MHz, MeOD) δ:8.58(s, 0.6H), 8.56(s, 0.4H), 7.65(m, 2H), 4.9-4.85(m, 1H), 4.78(d, J=9.5Hz, 0.5H), 4.74(d, J=9.3Hz, 0.5H), 4.25(t, 10.5Hz, 1H) ), 4.21(s, 0.5H), 4.16(s, 0.5H), 4.13(m, 1H), 3.85-3.71(m, 7H), 3.6-3.4(m, 2H), 3.25(s, 1.8H), 3.0(s, 1.2H), 2.13-1.92(m, 2H), 1.8 3-1.73(m, 1H), 1.62-1.55(m, 1H), 1.3(t, J=7.3Hz, 1.3H), 1.14(t, J=7.0Hz, 1.8H).

[0236] The following examples are prepared starting from tert-butylsulfanyl acetate, the corresponding cyclic ketones (intermediates 8, 9 and analogues) and intermediate 3 following the procedure described for example 2.41.201. LC-MS and Gal-3 inhibition data are listed in Table 5 below. The LC-MS conditions used are 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.

[0237] [Table 22]

[0238] [Table 23]

[0239] [Table 24]

[0240]

Table 25

[0241]

Table 26

[0242]

Table 27

[0243]

Table 28

[0244]

Table 29

[0245]

Table 30

[0246]

Table 31

[0247]

Table 32

[0248]

Table 33

[0249]

Table 34

[0250] [Table 35]

[0251] [Table 36]

[0252] [Table 37]

[0253] [Table 38]

[0254] [Table 39]

[0255] The following examples are prepared starting from tert-butylsulfanyl acetate, the corresponding ketone (Intermediate 7 and analogs) and Intermediate 3 following the procedures described for Example 2.41.201. The LC-MS and Gal-3 inhibition data are listed in Table 6 below. The LC-MS conditions used are 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.

[0256] [Table 40]

[0257] [Table 41]

[0258] [Table 42]

[0259] The following examples were prepared starting from tert-butylsulfanyl acetate, the corresponding aldehyde and intermediate 3 following the procedure described for example 2.41.201. The LC-MS and Gal-3 inhibition data are listed below in Table 7. The LC-MS conditions used were LC-MS(A).

[0260] [Table 43]

[0261] [Table 44]

[0262] Example 2.47.203. 2-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxy Methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-N-methylacetamide (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-2-oxoethyl)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 10 (0.06 g, 0.1 mmol) in DCM (3.0 mL) at rt is added methanesulfonyl chloride (0.007 mL, 1.2 eq) and DIPEA (0.041 mL, 0.17 mmol, 3.0 eq). The reaction mixture is stirred at rt for 2 h and 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 Na2SO4, filtered and the solvent is removed in vacuo to give a colourless oil. The crude is purified by preparative HPLC / MS (II) to recover the title compound as a white powder (0.06 g, 92%). LC-MS (A):t R =0.97min;[M+H] + :780.18.

[0263] 2-(((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)-N-ethyl-2-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-N-methylacetamide (2.47.203.) K2CO3 (0.001 g, 0.2 eq) is added to a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.03 g, 0.04 mmol) in MeOH (1.5 mL) at rt. The reaction mixture is stirred at rt for 17 h and then partitioned between MeCN and water. The mixture is directly purified by preparative HPLC / MS (II) and the title compound is recovered as a beige powder (0.024 g, 97%). LC-MS (A):t R =0.74min;[M+H] + :653.97. 1 H NMR (400MHz, MeOD) δ:8.56(m, 1H), 7.65(m, 2H), 4.9-4.75(m, 2H), 4.28-4.16(m, 2H), 4.13(m, 1H) , 3.9-3.71(m, 3H), 3.65-3.55(m, 3H), 3.55-3.45(m, 1H), 3.28(s, 0.8H), 3.24 (s, 1.2H), 3.15-3.05(m, 1H), 3.0(s, 0.5H), 2.97(s, 0.5H), 2.86(s, 3H), 2.35 -2.23(m, 1H), 2.4-1.9(m, 1H), 1.82-1.7(m, 2H), 1.3(m, 1.3H), 1.15(m, 1.8H).

[0264] Example 2.47.203R. (R)-2-(((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)-N-ethyl-2-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-N-methylacetamide Separation of the epimers of Example 2.47.203. (0.024 g) by chiral preparative HPLC (V) afforded the title compound (0.008 g) as a beige powder. R =2.66min.

[0265] Example 2.47.203S. 2-(((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)-N-ethyl-2-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-N-methylacetamide Separation of the epimers of Example 2.47.203. (0.024 g) by chiral preparative HPLC (V) afforded the title compound (0.008 g) as a beige powder. R =3.52min.

[0266] The following examples were prepared similarly to Example 2.47.203. starting from Intermediate 10, Intermediate 10AR, Intermediate 10AS, Intermediate 10I and the corresponding sulfonyl chloride, carbamoyl chloride and isocyanate. LC-MS and Gal-3 inhibition data are listed in Table 8 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.

[0267] [Table 45]

[0268] [Table 46]

[0269] [Table 47]

[0270] [Table 48]

[0271] [Table 49]

[0272] Example 2.41.232. 2R,3R,4S,5R,6S)-2-(Acetoxymethyl)-6-((2-(ethyl(phenyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate 1. N-Ethyl-N-phenyl-2-((tetrahydro-2H-pyran-2-yl)thio)acetamide N-ethyl-N-phenyl-2-((tetrahydro-2H-pyran-2-yl)thio)acetamide is prepared as a beige oil from 3,4-dihydro-2H-pyran, ethyl thioglycolate, N-ethylaniline and tetrahydro-4H-pyran-4-one according to the procedure described for intermediate 12. LC-MS (A): R =0.81;[M+H] + :296.15.

[0273] 2. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(phenyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)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 N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-mercapto-N-phenylacetamide (0.09 g, 0.3 mmol) in aq. 10% Na2CO3 (2.0 mL) is added TBAHS (0.62 g, 1.78 mmol, 6.0 eq). To this mixture is added intermediate 3 (0.22 g, 1.2 mmol, 1.2 eq) in EA (4.0 mL) and the mixture is stirred at rt for 15 h and diluted with EA (25.0 mL), water (25.0 mL) and brine (25.0 mL). The phases are separated and the aqueous layer is extracted with EA (50.0 mL). The combined organic phases are dried over Na2SO4, filtered and the solvent is removed under vacuum. The residue is purified by preparative HPLC / MS (I) to recover the title compound as a beige powder (0.06 g, 24%). LC-MS (A): R =1.05m in;[M+H] + :765.17.

[0274] 3. 2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-phenylacetamide (2.41.232.) K2CO3 (0.002 g, 0.014 mmol, 0.2 eq) is added at rt to a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-(ethyl(phenyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.055 g, 0.07 mmol) in MeOH (2.0 mL). The reaction mixture is stirred at rt for 15 h, quenched with MeCN and then water, and the mixture is directly purified by preparative HPLC / MS (I) to recover the title compound as a beige solid (0.040 g, 87%). LC-MS(A):t R =0.83min;[M+H] + :639.15. 1 H NMR (400MHz, MeOD) δ:8.51-8.62(m, 1H), 7.39-7.73(m, 7H), 4.75-4.82(m, 1H), 4.55-4.68(m, 0H), 4.33-4.41(m, 1H), 4.05-4.27(m, 2H) , 3.83-4.00(m, 1H), 3.65-3.80(m, 6H), 3.55-3.65(m, 1H), 3.40-3.54(m, 2H), 1.48-2.21(m, 4H), 1.08-1.26(m, 3H).

[0275] The following aryl / heteroaryl amides were prepared similarly to Example 2.41.232. starting from the corresponding 2-mercaptoacetamide (prepared similarly to Intermediate 12) and Intermediate 2 or Intermediate 14. LC-MS and Gal-3 inhibition data are listed in Table 9 below. LC-MS conditions used were LC-MS(A). Chiral HPLC (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0276] [Table 50]

[0277] [Table 51]

[0278] [Table 52]

[0279] [Table 53]

[0280] The following examples are prepared similarly to Example 2.41.232., starting from the corresponding 2-mercaptoacetamide (prepared similarly to Intermediate 12) and Intermediate 2 or Intermediate 14. LC-MS and Gal-3 inhibition data are listed in Table 10 below. LC-MS conditions used are LC-MS(A). Chiral HPLC (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0281] [Table 54]

[0282] [Table 55]

[0283] [Table 56]

[0284] [Table 57]

[0285] Example 10.41.203. 2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 13 (0.05 g, 0.10 mmol) in DMF (2.0 mL) is added 1-ethynyl-3,5-difluorobenzene (0.02 g, 0.15 mmol, 1.5 eq), CuI (0.006 g, 0.03 mmol, 0.3 eq) and DIPEA (0.05 mL, 0.30 mmol, 3.0 eq). The reaction mixture is stirred at 43 °C for 1 h, then cooled to rt, diluted with EA and filtered. The organic layer is washed with aq.sat. NH4Cl, brine, dried over Na2SO4, filtered and the solvent is removed under vacuum. The resulting crude is purified by preparative HPLC / MS (I) to give the title compound as a beige solid (0.06 g, 90%). LC-MS (A):t R =0.93min;[M+H] + :685.18.

[0286] 2. 2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide (10.41.203.) To a solution of 2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((2-(ethyl(methyl)amino)-1-(4-hydroxytetrahydro-2H-pyran-4-yl)-2-oxoethyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate (0.06 g, 0.09 mmol, 1.0 eq) in MeOH (3.0 mL) is added K2CO3 (0.003 g, 0.02 mmol, 0.2 eq). The reaction mixture is stirred at rt for 3 h, acetonitrile is added followed by water and the mixture is directly purified by preparative HPLC / MS (I) to give the title product as a beige solid (0.05 g, 91%). LC-MS (A):t R =0.67min;[M+H] + :559.22.

[0287] The following examples are prepared starting from intermediate 13 or a close analogue and the corresponding alkyne following the procedure described for Example 10.41.203. LC-MS and Gal-3 inhibition data are listed in Table 11 below. The LC-MS conditions used were LC-MS(A). Chiral HPLC (conditions and retention times) and inhibition data for the epimers R and S of selected examples are also listed.

[0288] [Table 58]

[0289] [Table 59]

[0290] [Table 60]

[0291] [Table 61]

[0292] Example 2.44.222.I. 2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(2-fluoro-2-methylpropyl)-2-(((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)-N-methylacetamide 1. tert-Butyl 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-mercaptoacetate tert-Butyl 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-mercaptoacetate is synthesized analogously to intermediate 7 from tert-butyl 2-sulfanylacetate and 4,4-difluorocyclohexan-1-one as a white solid. LC-MS (A) t R =0.94min, [M+H] + :283.17.

[0293] 2. tert-Butyl 2-(((2S,3R,4S,5R,6R)-5-acetoxy-6-(acetoxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4,4-difluoro-1-hydroxycyclohexyl)acetate To a solution of tert-butyl 2-(4,4-difluoro-1-hydroxycyclohexyl)-2-mercaptoacetate (0.12 g, 0.43 mmol) in aq. 10% Na2CO3 (4.0 mL) is added TBAHS (0.89 g, 2.55 mmol, 6.0 eq) followed by a solution of intermediate 14 (0.63 g, 0.50 mmol, 1.2 eq) in EA (10.0 mL). The reaction mixture is stirred at rt for 2 h, diluted with EA, water and brine and the phases are separated. The aqueous layer is extracted with EA, the organic phases are combined, dried over Na2SO4, filtered and the solvent is removed in vacuo to give a solid. Purification by preparative HPLC / MS (II) afforded the desired product as a white solid (0.22 g, 71%). LC-MS (A) t R =1.13min, [M+H] + :724.21.

[0294] 3. 2-(((2S,3R,4S,5R,6R)-5-acetoxy-6-(acetoxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4,4-difluoro-1-hydroxycyclohexyl)acetic acid To a solution of tert-butyl 2-(((2S,3R,4S,5R,6R)-5-acetoxy-6-(acetoxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4,4-difluoro-1-hydroxycyclohexyl)acetate (0.22 g, 0.30 mmol) in DCM (8.0 mL) is added TFA (0.39 mL, 5.11 mmol, 17.0 eq) and the reaction mixture is stirred at rt for 20 h. The mixture is neutralized with aq. 2M NaOH, diluted with DCM and the layers are separated. The aqueous layer is extracted with DCM (3x) and the combined organic layers are dried over Na2SO4, filtered and the solvent removed in vacuo to recover the title product as a beige powder (0.14 g, 68%) without further purification. LC-MS (A) t R =0.97min, [M+H] + :668.15.

[0295] 4. ((2R,3R,4S,5R,6S)-3-acetoxy-6-((1-(4,4-difluoro-1-hydroxycyclohexyl)-2-((2-fluoro-2-methylpropyl)(methyl)amino)-2-oxoethyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate To a solution of 2-(((2S,3R,4S,5R,6R)-5-acetoxy-6-(acetoxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4,4-difluoro-1-hydroxycyclohexyl)acetic acid (0.45 g, 0.58 mmol) in DMF (20.0 mL) is added HATU (0.25 g, 0.616 mmol, 1.05 eq), followed by a solution of 2-fluoro-N,2-dimethylpropan-1-amine HCl salt (0.1 g, 0.7 mmol, 1.2 eq) and DIPEA (0.27 mL, 1.58 mmol, 2.7 eq) in DMF (2.0 mL). The mixture is stirred at rt for 72 h, filtered and purified directly by preparative HPLC / MS (I) to give the title compound as a beige solid (0.14 g, 32%). LC-MS (A) t R =1.10min, [M+H] + :755.23.

[0296] 5. 2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(2-fluoro-2-methylpropyl)-2-(((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)-N-methylacetamide (2.44.222.I.) To a solution of ((2R,3R,4S,5R,6S)-3-acetoxy-6-((1-(4,4-difluoro-1-hydroxycyclohexyl)-2-((2-fluoro-2-methylpropyl)(methyl)amino)-2-oxoethyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate (0.142 g, 0.094 mmol) in MeOH (7.0 mL) is added K2CO3 (0.003 g, 0.02 mmol, 0.2 eq). After stirring at rt for 2 h, the reaction mixture is diluted with MeCN, then with water and directly purified by preparative HPLC / MS (I) to give the title compound as a beige solid (0.055 g, 88%). LC-MS(A) R =0.99min, [M+H] + :671.42.

[0297] Example 2.44.222R.I. ( R)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(2-fluoro-2-methylpropyl)-2-(((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)-N-methylacetamide [1,3-di-deoxy-1-((2-(4,4-difluoro-1-hydroxycyclohexyl)-(N-(3-fluoro-3-methylbutyl))-N-methylacetamide)-(R)-thio)-2-O-methyl-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-bD-galactopyranoside] Separation of the epimers of Example 2.44.222.I. (0.055 g) by chiral preparative HPLC (VI) afforded the title compound (0.024 g) as a white solid. R =1.62min.

[0298] Example 2.44.222S.I. ( S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(2-fluoro-2-methylpropyl)-2-(((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)-N-methylacetamide [1,3-di-deoxy-1-((2-(4,4-difluoro-1-hydroxycyclohexyl)-(N-(3-fluoro-3-methylbutyl))-N-methylacetamide)-(S)-thio)-2-O-methyl-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-bD-galactopyranoside] Separation of the epimers of Example 2.44.222.I. (0.055 g) by chiral preparative HPLC (VI) afforded the title compound (0.016 g) as a white solid. R =2.24min. 1H NMR (400MHz, MeOD) δ:8.68(s, 0.8H), 8.66(s, 0.2H), 7.68(m, 2H), 4.95(dd, J1=10.8Hz, J2=3.3Hz, 1H), ), 4.85(d, J=9.5Hz, 1H), 4.3(s, 1H), 4.1(d, J=2.3Hz, 1H), 4.0-3.93(m, 1H), 3.85-3.6(m, 5H), 3.7(s, 0.8H), 3.5(s, 2.3H), 3.55(s, 3H) 2.4-1.7(m, 8H), 1.5-1.3(m, 6H).

[0299] The following examples are prepared starting from 2-(((2S,3R,4S,5R,6R)-5-acetoxy-6-(acetoxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4,4-difluoro-1-hydroxycyclohexyl)acetic acid (Example 2.44.222.I., step 3.) and the corresponding secondary and primary amines according to the procedure described for Example 2.44.222.I. LC-MS and Gal-3 inhibition data are listed in Table 12 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.

[0300] [Table 62]

[0301] [Table 63]

[0302] [Table 64]

[0303] [Table 65]

[0304] [Table 66]

[0305] [Table 67]

[0306] [Table 68]

[0307] [Table 69]

[0308] Example 2.67.226.I. 1-(4,4-difluoropiperidin-1-yl)-2-(((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-(6-hydroxyspiro[2.5]octan-6-yl)ethan-1-one 1. 1-(4,4-difluoropiperidin-1-yl)-2-(6-hydroxyspiro[2.5]octan-6-yl)-2-mercaptoethan-1-one 1-(4,4-Difluoropiperidin-1-yl)-2-(6-hydroxyspiro[2.5]octan-6-yl)-2-mercaptoethan-1-one is synthesized as a beige solid from 3,4-dihydro-2H-pyran, ethyl 2-mercaptoacetate, 4,4-difluoropiperidine and spiro[2.5]octan-6-one according to the procedure described for the synthesis of intermediate 12. LC-MS (A) t R =0.95min, [M+H] + :320.15.

[0309] 2. ((2R,3R,4S,5R,6S)-3-acetoxy-6-((2-(4,4-difluoropiperidin-1-yl)-1-(6-hydroxyspiro[2.5]octan-6-yl)-2-oxoethyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate ((2R,3R,4S,5R,6S)-3-acetoxy-6-((2-(4,4-difluoropiperidin-1-yl)-1-(6-hydroxyspiro[2.5]octan-6-yl)-2-oxoethyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate was prepared in step 1 of this experiment using 1-(4,4-difluoropiperidin-1-yl)-2-(6-hydroxyspiro[2.5]octan-6-yl) -2-mercaptoethan-1-one and intermediate 14 as a beige solid according to the procedure described for the synthesis of intermediate 13. LC-MS (A) t R =1.13min, [M+H] + :761.26.

[0310] 3. 1-(4,4-difluoropiperidin-1-yl)-2-(((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-(6-hydroxyspiro[2.5]octan-6-yl)ethan-1-one (2.67.226.I.) To a solution of ((2R,3R,4S,5R,6S)-3-acetoxy-6-((2-(4,4-difluoropiperidin-1-yl)-1-(6-hydroxyspiro[2.5]octan-6-yl)-2-oxoethyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate (0.05 g, 0.07 mmol, 1.0 eq) in MeOH (3.0 mL) is added K2CO3 (0.002 g, 0.01 mmol, 0.2 eq) at rt. The reaction mixture is stirred at rt for 90 min and then diluted with MeCN and then with water. The mixture is directly purified by preparative HPLC / MS (I) to give the title compound as a beige solid (0.04 g, 79%). R =1.02min, [M+H] + :677.19.

[0311] The following examples were prepared similarly to Example 2.67.226.I., starting from 1-(4,4-difluoropiperidin-1-yl)-2-((tetrahydro-2H-pyran-2-yl)thio)ethan-1-one (synthesized similarly to Intermediate 12, steps 1.-3.), the corresponding ketone and Intermediate 14. The LC-MS and Gal-3 inhibition data are listed in Table 13 below. The LC-MS conditions used are LC-MS(A). Chiral HPLC (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0312] [Table 70]

[0313] [Table 71]

[0314] [Table 72]

[0315] [Table 73]

[0316] Example 2.44.226.II. 2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((2S,3R,4S,5R,6R)-3-ethoxy-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)ethan-1-one Example 2.44.226.II. is prepared from 2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-mercaptoethan-1-one (prepared similarly to intermediate 11) and intermediate 15 as a beige solid, similarly to example 2.67.226.I. LC-MS (A):t R = 1.0 min; [M+H] + :701.21.

[0317] The LC-MS and Gal-3 inhibition data for Example 2.44.226.II. is set forth below in Table 14. The LC-MS conditions used were LC-MS(A).

[0318] [Table 74]

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

[0320] [Table 75]

[0321] [Table 76]

[0322] 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).

[0323] 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.

[0324] Plates are incubated for 3 h at 4 °C, then washed with cold assay buffer (3x50 μl), incubated with 25 μL / well of streptavidin-peroxidase solution (diluted to 80 ng / ml in assay buffer) for 1 h at 4 °C, then washed further with assay buffer (3x50 μl). Finally, 25 μL / well of ABTS substrate is added. OD (410 nm) is recorded after 30-45 min and IC 50 Calculate the value.

[0325] 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, R １ teeth, - structure: 【Chemistry 2】 represents an amide group; -- R Ｎ１１ teeth, --- -C １－６ - alkyl; --- -CH ２ -CH ２ -O-C １－３ - alkyl; --- -CH ２ -C １－３ -fluoroalkyl; --- -C ０－２ -Alkylene-C ３－６ -cycloalkyl, ３－６ -cycloalkyl is unsubstituted or substituted by one or two fluoro or methyl groups; ０－２ -Alkylene-C ３－６ -cycloalkyl; --- -C ０－２ -Alkylene-C ４－６ -cycloalkyl, ４－６ -cycloalkyl has one oxygen ring atom, -C ０－２ -Alkylene-C ４－６ -cycloalkyl; --- -CH ２ -CH ２ -NR Ｎ２１ R Ｎ２２ (R Ｎ２１ and R Ｎ２２ together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl selected from azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, and morpholin-4-yl; or --- -C １－２ -Alkylene-R １１ (R １１ represents phenyl or a 5- or 6-membered heteroaryl, which is independently unsubstituted or substituted with one methyl; --- phenyl or 5- or 6-membered heteroaryl, which phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted by one methyl; or 【Chemistry 3】 represents; And R Ｎ１２ is hydrogen or C １－２ - represents alkyl; -- or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl selected from azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl, which 4- to 6-membered heterocyclyl is independently unsubstituted or substituted with 1 or 2 substituents which are independently methyl or fluoro; -- or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached form morpholin-4-yl; -- or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached form a partially aromatic bicyclic ring consisting of pyrrolidin-1-yl or piperidin-1-yl, the pyrrolidine or piperidine being fused to a phenyl ring; Ar １ teeth, --phenyl, substituted with 1, 2, 3, 4 or 5 substituents, said substituents being independently selected from halogen, methyl, cyano and methoxy; represents; - R ２ａ represents hydrogen; and R ２ｂ teeth, -- -C ２－４ - alkyl; -- -C ０－１ -Alkylene-Ar ２ｂ (Ar ２ｂ represents phenyl or a 5- or 6-membered heteroaryl, which is independently unsubstituted or substituted by 1 or 2 methyl; represents; - or R ２ａ and R ２ｂ each represents hydrogen, methyl, ethyl, or n-propyl; - or R ２ａ and R ２ｂ along with the carbon atoms to which they are attached. -- C ３－６ -Cycloalkylene (the C ３－６ -Cycloalkylene is independently an unsubstituted substituted or substituted with 1 or 2 substituents, the substituents being independently methyl or fluoro; --tetrahydro-2H-pyran-4,4-diyl, which is unsubstituted or substituted by 2 or 4 methyl; 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 substituted by --C １－３ -alkyl, -C ０－２ -Alkylene-C ３－６ -cycloalkyl or -L-R Ｎ２ ( --- -L- is -CO-, -SO ２ --, ＊ —CO—NH—, ＊ -CO-O- or ＊ -SO ２ represents —NH—, --- R Ｎ２ 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 - R ２ａ and R ２ｂ Together with the carbon atoms to which they are attached, the structure (S ２ＡＢ ) spiro-bicyclic ring system 【Chemistry 4】 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 ３ is hydroxy or C １－３ - represents alkoxy.

2. Formula (I Ｓ 2. A compound of formula (I) as defined in claim 1, which is also a compound of the formula: 【Chemistry 5】 (wherein the group R １ The carbon atom to which is attached is represented by formula (I Ｓ ) 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 6】 (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. R １ But the structure 【Chemistry 7】 represents an amide group; - R Ｎ１１ but, -- -C １－６ - alkyl; -- --CH ２ -C １－３ -fluoroalkyl; --Cyclopropyl, cyclobutyl, --CH ２ -Cyclopropyl, -CH ２ -Cyclopentyl, -CH ２ -1-fluorocyclopentyl or -CH ２ -CH ２ -cyclopropyl; -- --CH ２ -3,3-difluorocyclobutyl; -- --CH ２ -Tetrahydro-2H-pyran-4-yl or -CH ２ -CH ２ -tetrahydro-2H-pyran-4-yl; -- tetrahydro-2H-pyran-4-yl or oxetan-3-yl; --benzyl; --phenyl or pyridinyl; Or, 【Chemistry 8】 represents; and, R Ｎ１２ is hydrogen or C １－２ - represents alkyl; - or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached form a 4-6 membered heterocyclyl selected from: azetidin-1-yl, unsubstituted or substituted at the 3-position with two fluoro; pyrrolidin-1-yl, unsubstituted or substituted at the 3-position with two fluoro; and piperidin-1-yl, unsubstituted or substituted at the 3- or 4-position with two fluoro; - or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached form morpholin-4-yl; - or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached form an indolin-1-yl ring; The compound according to any one of claims 1 to 4, or a pharma- ceutically acceptable salt thereof.

6. R １ But the structure 【Chemistry 9】 represents an amide group; - R Ｎ１１ but, -- -C １－６ - alkyl; -- --CH ２ -CH ２ -O-C １－３ - alkyl; -- --CH ２ -C １－３ -fluoroalkyl; Or, --Cyclopropyl, cyclobutyl, --CH ２ -Cyclopropyl, -CH ２ -Cyclopentyl, -CH ２ -1-fluorocyclopentyl or -CH ２ -CH ２ -cyclopropyl; represents; and, R Ｎ１２ C １－２ - represents alkyl; The compound according to any one of claims 1 to 4, or a pharma- ceutically acceptable salt thereof.

7. - R ２ａ represents hydrogen; and R ２ｂ but, -- -C ２－４ - alkyl; --benzyl; --phenyl unsubstituted or substituted by one or two methyls; Or, -- 5-membered heteroaryl unsubstituted or substituted by one methyl; represents; - or R ２ａ and R ２ｂ each represents methyl, ethyl or n-propyl; - or R ２ａ and R ２ｂ together with the carbon atoms to which they are attached, -- C ４－６ -Cycloalkylene (the C ４－６ -Cycloalkylene is independently an unsubstituted substituted or substituted with 1 or 2 substituents, the substituents being independently methyl or fluoro; -- tetrahydro-2H-pyran-4,4-diyl; Or, -- 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; --Azetidine-3,3-diyl (the nitrogen of the azetidine is --CO-O-C １－３ -substituted by alkyl; or forming a 3- to 6-membered ring selected from Or, - R ２ａ and R ２ｂ along with the carbon atoms to which they are attached: 【Chemistry 10】 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 ３ 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: (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-isobutyl-N-methylacetamide; (S)-2-(((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-hydroxy-N,N,3-trimethylbutanamide; (S)-2-(((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)-N-ethyl-3-hydroxy-N,3-dimethylbutanamide; (S)-2-(((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)-N,N-diethyl-3-hydroxy-3-methylbutanamide; (S)-2-(((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-hydroxy-3-methyl-1-((R)-2-methylazetidin-1-yl)butane-1- on; (S)-2-(((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-hydroxy-3-methyl-1-((S)-2-methylazetidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-3-methyl-1-(3-methylazetidin-1-yl)butan-1-one; (S)-1-(azetidin-1-yl)-2-(((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-hydroxy-3-methylbutan-1-one; (S)-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-N-isobutyl-N-methylacetamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxy-1-methylpiperidin-4-yl)-N-methylacetamide; (S)—N-benzyl-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-1-(piperidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxy-1-methylpiperidin-4-yl)-1-(indolin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N,N-dimethylacetamide; (S)-2-(((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)-N,N-diethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxy hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-((R)-2-methylazetidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-((S)-2-methylazetidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(3-methylazetidin-1-yl)ethan-1-one; (S)-1-(azetidin-1-yl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)ethan-1-one; (S)—N-benzyl-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(piperidin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(indolin-1-yl)ethan-1-one; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(thiophen-2-ylmethyl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-1-(pyrrolidin-1-yl)ethan-1-one; (S)—N-(cyclopentylmethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxy hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-((1-methyl-1H-imidazol-4-yl)methyl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)acetamide; (S)—N-(2-cyclopropylethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)—N-(cyclopropylmethyl)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(((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)-N-ethyl-2-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclohexyl)-1-(piperidin-1-yl)ethan-1-one; (S)-2-(((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-( 1-hydroxycyclohexyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)—N-cyclobutyl-2-(((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-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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)-N-(2-fluoro-2-methylpropyl)-2-(1-hydroxycyclohexyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclohexyl)-N-methyl-N-(pyridin-2-ylmethyl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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) -N,N-dimethylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-ethyl-N-methylacetamide; (S)-N-cyclobutyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-1-(piperidin-1-yl)ethan-1-one; (S)—N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(2-fluoro-2-methylpropyl)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-((1-fluorocyclopentyl)methyl)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(3,3-dimethylbutyl)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(3,3-difluoroazetidin-1-yl)-2-(((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)ethan-1-one; (S)-2-(((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)-N-ethyl-2-(1-hydroxycyclopentyl)-N-methylacetamide; (S)-1-(azetidin-1-yl)-2-(((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-(1-hydroxycyclopentyl)ethan-1-one; (S)-2-(((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-(1-hydroxycyclopentyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)—N-cyclobutyl-2-(((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-(1-hydroxycyclopentyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclopentyl)-N-methyl-N-neopentylacetamide; (S)-2-(((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)-N-ethyl-2-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-1-(azetidin-1-yl)-2-(((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-(1-hydroxycyclobutyl)ethan-1-one; (S)-2-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxy hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-(1-hydroxycyclobutyl)-1-(piperidin-1-yl)ethan-1-one; (S)—N-(cyclopropylmethyl)-2-(((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-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclobutyl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(((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)-N-(2-fluoro-2-methylpropyl)-2-(1-hydroxycyclobutyl)-N-methylacetamide; (S)-2-(((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-(1-hydroxycyclobutyl)-N-methyl-N-neopentylacetamide; (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)-N-ethyl-N-methylacetamide; (S)-1-(azetidin-1-yl)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)ethan-1-one; (S)—N-(cyclopropylmethyl)-2-(3,3-difluoro-1-hydroxycyclobutyl)-2-(((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)-N-methylacetamide; (S)-2-(((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)-N,3-diethyl-3-hydroxy-N-methylpentanamide; (S)—N-(cyclopropylmethyl)-2-(((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-ethyl-3-hydroxy-N-methylpentanamide; (S)-2-(((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-ethyl-N-(2-fluoro-2-methylpropyl)-3-hydroxy-N-methylpentanamide; (S)—N-benzyl-2-(((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-hydroxy-N,3-dimethylbutanamide; (S)-2-(((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-hydroxy-3-methyl-1-(piperidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-3-methyl-1-(pyrrolidin-1-yl)butan-1-one; (S)-2-(((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-hydroxy-N,3-dimethyl-N-((1-methyl-1H-imidazol-4-yl)methyl)butanamide; (S)—N-(cyclopropylmethyl)-2-(((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-hydroxy-N,3-dimethylbutanamide; (S)-2-(((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-hydroxy-N,3-dimethyl-N-neopentylbutanamide; (S)-2-(((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-hydroxy-N-(2-methoxyethyl)-N,3-dimethylbutanamide; (S)-2-(((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-hydroxy-N,3-dimethyl-N-(2-morpholinoethyl)butanamide; (2S,3R)-2-(((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)-N-ethyl-3-hydroxy-N-methylpentanamide; (2S,3S)-2-(((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)-N-ethyl-3-hydroxy-N-methylpentanamide; (2S,3R)-1-(azetidin-1-yl)-2-(((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-hydroxypentan-1-one; (2S,3S)-1-(azetidin-1-yl)-2-(((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-hydroxypentan-1-one; (2S,3R)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methylpentanamide; (2S,3S)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methylpentanamide; (2S,3R)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-4-phenylbutanamide; (2S,3S)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-4-phenylbutanamide; (2S,3R)-1-(azetidin-1-yl)-2-(((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-hydroxy-4-phenylbutan-1-one; (2S,3S)-1-(azetidin-1-yl)-2-(((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-hydroxy-4-phenylbutan-1-one; (2S,3R)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-4-phenylbutanamide; (2S,3S)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-4-phenylbutanamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)-N-methylacetamide; (S)-2-(1-(cyclopropylsulfonyl)-4-hydroxypiperidin-4-yl)-2-(((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)-N-ethyl-N-methylacetamide; Methyl 4-((S)-1-(((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-(ethyl(methyl)amino)-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate; (2S,3R)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; (2S,3S)-2-(((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)-N-ethyl-3-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; (2S,3R)-1-1-(azetidin-1-yl)-2-(((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-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)propan-1-one; (2S,3S)-1-(azetidin-1-yl)-2-(((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-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)propan-1-one; (2S,3R)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; (2S,3S)-N-(cyclopropylmethyl)-2-(((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-hydroxy-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)propanamide; (S)—N-cyclopropyl-4-(1-(((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-(ethyl(methyl)amino)-2-oxoethyl)-4-hydroxypiperidine-1-carboxamide; (S)—N-(cyclopropylmethyl)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(oxetan-3-yl)acetamide; (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-2-(ethyl(methyl)amino)-1-(3-hydroxy-1-(methoxycarbonyl)azetidin-3-yl)-2-oxoethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate; N-cyclopropyl-4-((S)-2-(ethyl(methyl)amino)-1-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy c-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)-2-oxoethyl)-4-hydroxypiperidine-1-carboxamide; (S)-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-phenylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-phenylacetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(pyridin-2-yl)acetamide; (S)-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methyl-N-(pyridin-3-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(pyridin-2-yl)acetamide; (S)—N-cyclobutyl-2-(((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)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)acetamide; (S)—N-cyclobutyl-2-(((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-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)acetamide; (S)—N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide; (S)-N-benzyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-((3,3-difluorocyclobutyl)methyl)-N-ethyl-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-(tetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)—N-ethyl-2-(((2S,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromothiazol-2-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-( ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)-2-(((2S,3R,4S,5R,6R)-4-(4-(3-cyano-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-ethyl-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)—N-ethyl-2-(((2S,3R,4S,5R,6R)-4-(4-(3-fluoro-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-2-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-methylacetamide; (S)—N-cyclopropyl-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((2S,3R,4S,5R,6R)-4-(4-(6-fluoro-5-methylpyridin-3-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)thio)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(2-fluoro-2-methylpropyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; (S)-N-(cyclopropylmethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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) -N,N-dimethylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-ethyl-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-isopropyl-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-dimethylbutyl)-2-(((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)-N-methylacetamide; (S)—N-(2-cyclopropylethyl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-difluorocyclobutyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(oxetan-3-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazolidine (1-yl)tetrahydro-2H-pyran-2-yl)thio)-1-morpholinoethan-1-one; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-dimethylpiperidin-1-yl)-2-(((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)ethan-1-one; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(4,4-dimethylcyclohexyl)-2-(((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)-N-methylacetamide; (S)—N-(bicyclo[1.1.1]pentan-1-yl)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-methylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(tetrahydro-2H-pyran-4-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-(pentan-3-yl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((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)-N-isopropylacetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-dimethylbutyl)-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(3,3-difluorocyclobutyl)-2-(((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)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-2-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazolidine (1-yl)tetrahydro-2H-pyran-2-yl)thio)-N-(2,2,2-trifluoroethyl)acetamide; (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-N-(4,4-dimethylcyclohexyl)-2-(((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)acetamide; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(6-hydroxyspiro[2.5]octan-6-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(1-hydroxy-4,4-dimethylcyclohexyl)-2-(((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)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(7-hydroxyspiro[3.5]nonan-7-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(7-hydroxy-2-oxaspiro[3.5]nonan-7-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(8-hydroxyspiro[4.5]decan-8-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-(((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-(9-hydroxy-3-oxaspiro[5.5]undecan-9-yl)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(((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)ethan-1-one; (S)-1-(4,4-difluoropiperidin-1-yl)-2-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(((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)ethan-1-one; (2S)-2-(1,1-difluoro-6-hydroxyspiro[2.5]octan-6-yl)-1-(4,4-difluoropiperidin-1-yl)-2-(((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)ethan-1-one; Or, (S)-2-(4,4-difluoro-1-hydroxycyclohexyl)-1-(4,4-difluoropiperidin-1-yl)-2-(((2S,3R,4S,5R,6R)-3-ethoxy-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)ethan-1-one; 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 pharma- ceutically acceptable salt thereof, for use as a medicament.

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. 10. 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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