2-Hydroxycycloalkane-1-carbamoyl derivatives

Abstract

The present invention is 1 , Ar 2 , L, n and R 1 The present invention relates to compounds of formula (I), as described herein, their preparation, pharmaceutically acceptable salts thereof, and their use as medicaments, pharmaceutical compositions comprising one or more compounds of formula (I), and their use, in particular as galectin-3 inhibitors. [Formula 1] TIFF2022544248000067.tif78170

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). Human, mouse and rat genome sequences 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: These include prototypical galectins, which have a single carbohydrate-recognition domain (CRD); chimaera galectins, which consist of unusual tandem repeats of proline- and glycine-rich short stretches fused to a 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 divalently or multivalently, e.g., cross-linking cell surface glycoconjugates, triggering 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;SharmaGal-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] 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. Summary of the Invention

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

[0011] [ka] (In the formula, n represents the integer 1 or 2 (particularly, n is 1); Ar 1 teeth, - aryl (especially phenyl) which is substituted by 1, 2, 3, 4 or 5 substituents (especially substituted by 1, 2 or 3 substituents), the substituents being halogen; methyl; cyano; methoxy; trifluoromethyl; trifluoromethoxy; NR N11 R N12 (R N11 represents hydrogen, and R N12 is hydroxy-C 2-3 -alkyl (especially 3-hydroxy-prop-1-yl) or R N11 and R N12 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl (particularly morpholin-4-yl) selected from morpholin-4-yl, azetidin-1-yl, pyrrolidin-1-yl and piperidin-1-yl, which 4- to 6-membered heterocyclyl is unsubstituted or substituted by one hydroxy; aryl (particularly phenyl); [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, said para substituent is preferably selected from halogen, methyl, cyano and methoxy; if a meta substituent is present, said meta substituent is preferably halogen.]; - 5- or 6-membered heteroaryl (especially thiazolyl), which is independently unsubstituted or substituted by 1 or 2 substituents, said substituents being independently selected from halogen, methyl, cyano and methoxy; or - 9- or 10-membered heteroaryl (especially benzothiazolyl), which 9- or 10-membered heteroaryl is independently unsubstituted or substituted by one methyl; represents; R 1 teeth, - Hydroxy; - C 1-3 - alkoxy (especially methoxy); - -O-CO-C 1-3 -alkyl; - -O-CH2-CH2-OH; or - -O-CH2-CO-R 1X (R 1X teeth, -- -hydroxy; --morpholin-4-yl; or -- -NR N21 R N22 (R N21 and R N22 are identical to the nitrogen atom to which they are attached. together form a 4- to 6-membered heterocyclyl selected from azetidin-1-yl, pyrrolidin-1-yl and piperidin-1-yl, the 4- to 6-membered heterocyclyl being substituted by one hydroxyl; represents ); represents; L represents a direct bond, methylene or ethylene (particularly a direct bond or methylene); Ar 2 teeth, - phenyl or 5- or 6-membered heteroaryl (in particular furanyl, thiophenyl, pyrrolyl, thiazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl or pyrimidinyl), which phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1, 2 or 3 substituents (in particular substituted by 1 or 2 substituents), said substituents being selected from the group consisting of C 1-6 -Alkyl, C 3-6 -Cycloalkyl, -CH2-C 3-6 -Cycloalkyl, C 1-3 -fluoroalkyl, C 1-3 -Fluoroalkoxy, C 1-3- phenyl or 5- or 6-membered heteroaryl, independently selected from alkoxy, halogen, morpholin-4-yl, amino, ethynyl and cyano (in particular furanyl, thiophenyl, pyrrolyl, thiazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl or pyrimidinyl); - a 9-membered bicyclic heteroaryl (particularly indolyl or benzothiophenyl, benzothiazolyl or benzimidazolyl) or a 10-membered bicyclic heteroaryl (particularly quinolinyl or quinoxalinyl), which 9 or 10-membered bicyclic heteroaryl is independently unsubstituted or substituted by 1 or 2 substituents, said substituents being independently selected from methyl, methoxy and halogen (particularly fluoro, chloro); or - Naphthyl; represents.)

[0012] The compounds of formula (I) have five chiral or asymmetric centers located in the tetrahydropyran moiety and two chiral or asymmetric centers located in the cycloalkane moiety, the latter being in the absolute (S,S)-configuration as described in formula (I). In addition, the compounds of formula (I) may contain one, and possibly more, chiral or asymmetric centers, such as one or more additional asymmetric carbon atoms. Thus, the compounds of formula (I) may exist as a mixture of stereoisomers or, preferably, as pure stereoisomers. The mixture of stereoisomers may be separated by methods known to those skilled in the art.

[0013] When a particular compound (or generic structure) is described as being in a particular absolute configuration, e.g., (R)- or (S)-enantiomer, such description is understood to mean the respective compound (or generic structure) in enriched, especially essentially pure, enantiomeric form. Similarly, when a particular asymmetric center of a compound is described as being in the (R)- or (S)-configuration, or in a particular relative configuration, such description is understood to mean said compound in enriched, especially essentially pure form, with respect to each configuration of said asymmetric center. Similarly, two chiral centers, e.g., in a cyclic group, may be present in a particular relative configuration. Thus, the description of cis or trans (or (R) as used, e.g., for a particular intermediate of a compound of the invention) is not intended to be limiting. * ,R * The description (R ) is understood to mean each stereoisomer of each relative configuration in enriched, in particular essentially pure, form. Thus, for a molecule or group, (R * ,R * ), unless expressly stated otherwise, encompasses the individual (R,R)-enantiomers, the (S,S)-enantiomers and any mixtures of these two enantiomers, including racemates.

[0014] 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).

[0015] 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.

[0016] The present invention also relates to isotopically labeled, especially2 H (deuterium)-labeled compounds of formula (I) according to embodiments 1) to 20), which are identical to compounds of formula (I) except that one or more atoms are respectively replaced by atoms having the same atomic number but an atomic mass different from that normally found in nature. Isotopically labeled compounds, especially 2 H (deuterium) labeled compounds of formula (I), (II) and (III) and salts thereof are 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.

[0017] In this patent application, bonds drawn as dotted lines indicate the point of attachment of the depicted group. For example, the group

[0018] [ka] is a 3-fluorophenyl group.

[0019] 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.

[0020] Any reference to compounds of formula (I) according to embodiments 1) to 20) will, where appropriate, be understood to also refer to the salts (especially the pharma- ceutically acceptable salts) of such compounds.

[0021] The term "pharmaceutically acceptable salt" refers to a salt that retains the desired biological activity of the subject compound and exhibits minimal undesired toxicological effects. Such salts include inorganic or organic acid and / or base addition salts, depending on the presence of basic and / or acidic groups in the subject compound. For reference, see, for example, "Handbook of Pharmaceut ical Salts.Properties, Selection and Use.'', P. Heinrich Stahl, Camille G. Wermuth (Eds.), Wiley-VCH, 2008; and ``Pharmaceutical Salts and Co-crystals'', Johan Wouters and Luc. See Quere (Eds.), RSC Publishing, 2012.

[0022] The definitions set forth herein are uniformly applied to the compounds of formula (I) defined in any one of embodiments 1) to 18) and apply mutatis mutandis throughout the specification and claims unless a broader or narrower definition is given by a specific definition. It is understood that a definition or preferred definition of a term may independently (and together) define and replace the respective term in any or all other terms or preferred definitions defined herein.

[0023] 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:

[0024] [ka] can be named (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-phenyl-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carbonyl or, alternatively, 1,3-di-deoxy-3-[4-phenyl-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside-1-carbonyl, where the absolute configuration of the carbon atom bearing the carbonyl group, which is the point of attachment to the rest of the molecule, is in the (2R)- or beta-configuration. For example, the compound (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-pyrrol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide is understood to also be called: 1,3-di-deoxy-2-O-methyl-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-(N-((1-methyl-1H-pyrrol-2-yl)methyl)-N-((1S,2S)-2-hydroxycyclohexyl))-β-D-galacto-pyranose-1-carboxamide.

[0025] Whenever a substituent is described as optional, such substituent may be absent. Often (i.e., each residue is unsubstituted with respect to any such substituent), in which case it is understood that all sites having a free valence (e.g., in an aromatic ring, to which such optional substituents may be attached, such as ring carbon atoms and / or ring nitrogen atoms having a free valence) are replaced with hydrogen as the case may be. Similarly, when the term "optionally" is used with respect to (ring) heteroatoms, this term means that each optional heteroatom, etc. is not present (i.e., a group has no heteroatoms / is a carbocyclic ring / etc.) or that each optional heteroatom, etc. is present as expressly defined. Groups defined herein are unsubstituted unless expressly defined otherwise in each embodiment or claim.

[0026] The term "halogen" means fluorine, chlorine or bromine, preferably fluorine or chlorine.

[0027] 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. Methyl is preferred. 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. (Phenyl or 5- or 6-membered heteroaryl)Ar 2 The substituent of "C 1-6 When expressing "-alkyl", this term means in particular methyl, ethyl or isopropyl; especially methyl.

[0028] "-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- (or ethylene) means -CH2-CH2-.

[0029] 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.

[0030] The term "fluoroalkyl", used alone or in combination, means an alkyl group as defined above having one to three carbon atoms in which one or more, and optionally all, hydrogen atoms have been replaced by fluorine. x-y The term "fluoroalkyl" (x and y are each integers) refers to a fluoroalkyl group as defined above having x to y carbon atoms. For example, C 1-3 -Fluoroalkyl groups have 1 to 3 carbon atoms and 1 to 7 hydrogen atoms are replaced by fluorine. Representative examples of fluoroalkyl groups include trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl and 2,2,2-trifluoroethyl. Trifluoromethyl is preferred.

[0031] 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-yThe 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.

[0032] 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 and cyclohexyl. Preference is given to cyclopropyl.

[0033] 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 1 "C 1-3 When referring to "alkoxy", the term specifically refers to methoxy. (phenyl or 5- or 6-membered heteroaryl)Ar 2 The substituent of "C 1-3 When referring to "-alkoxy", the term specifically refers to methoxy.

[0034] The term "heterocyclyl", whether used alone or in combination, unless expressly defined broader or narrower, means a saturated or unsaturated non-aromatic monocyclic hydrocarbon ring having one or two ring heteroatoms independently selected from nitrogen, sulfur and oxygen (particularly one oxygen atom, one sulfur atom, one nitrogen atom, two nitrogen atoms, two oxygen atoms, one nitrogen atom and one oxygen atom). x-y The term "-heterocyclyl" means such a heterocycle having from x to y ring atoms. Heterocyclyl groups are unsubstituted or substituted as explicitly defined.

[0035] The term "aryl", used alone or in combination, means phenyl or naphthyl, preferably phenyl, said aryl groups being unsubstituted or substituted as expressly defined.

[0036] 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, etc. , benzofuranyl, isobenzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, 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 Ar representing "5- or 6-membered heteroaryl" 2 In the context of the term, this term means in particular furanyl, thiophenyl, pyrrolyl, thiazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl or pyrimidinyl; especially furan-2-yl, thiophen-2-yl, thiophen-3-yl, 1H-pyrrol-2-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-4-yl, isothiazol-5-yl, isoxazol-4-yl, 1H-pyrazol-3-yl, 1H-pyrazol-5-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl or pyrimidin-5-yl. 2 With respect to the term, in particular, it means indolyl; or, in addition, benzothiophenyl, benzothiazolyl or benzimidazolyl; especially 1H-indol-2-yl; or, in addition, benzothiophen-6-yl, benzothiazol-6-yl, benzothiazol-5-yl or benzimidazol-6-yl; said 9-membered bicyclic heteroaryl being unsubstituted or substituted as expressly defined; a specific example is 1-methyl-1H-indol-2-yl. The substituent Ar representing "10-membered bicyclic heteroaryl" 2In the context of the term this means in particular quinolinyl or quinoxalinyl; especially quinolin-2-yl or quinoxalin-5-yl.

[0037] The term "cyano" refers to the group --CN.

[0038] 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.

[0039] 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.

[0040] Further aspects of the invention are described below: 2) The second embodiment is 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).

[0041] 3) In another embodiment, Ar 1 represents phenyl substituted by 1, 2 or 3 substituents; one of the substituents is attached at the meta position of the phenyl and the substituent is halogen; the remaining substituents, if present, are halogen (especially fluoro); or - one of the substituents is attached at the para position of the phenyl, and the substituents are independently selected from methyl, cyano, and methoxy; Any remaining substituents, if present, are halogen (especially fluoro); It relates to compounds according to embodiment 1).

[0042] 4) In another embodiment, Ar 1 The structure:

[0043] [ka] (In the formula, - R o1 represents hydrogen, fluoro, methyl, methoxy or trifluoromethyl; - R m1 represents hydrogen or halogen; - R p represents hydrogen, halogen, methyl, cyano, 3-hydroxyprop-1-yl or morpholin-4-yl; - R m2 represents hydrogen, halogen, methyl, methoxy or trifluoromethoxy; It relates to compounds according to embodiment 1), in which

[0044] 5) In another embodiment, Ar 1 The structure:

[0045] [ka] (In the formula, - R m2 represents hydrogen or fluoro; and Rp 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), in which

[0046] 6) In another embodiment, Ar 1 The structure:

[0047] [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), in which

[0048] 7) In another embodiment, Ar 1 but:

[0049] [ka]

[0050] [ka]

[0051] [ka] for the compound according to embodiment 1), Each of the above groups A) to C) forms a specific subembodiment; group A) forms another subembodiment.

[0052] 8) In another embodiment, R 1 but, - Hydroxy; - methoxy; or - -O-CH2-CO-R 1X (R 1X teeth, -- -hydroxy; --morpholin-4-yl; or

[0053] [ka] represents ); represents; relating to a compound according to any one of embodiments 1) to 7).

[0054] 9) In another aspect, R 1 represents hydroxy; relates to compounds according to any one of embodiments 1) to 7).

[0055] 10) In another aspect, R 1 represents methoxy; relates to compounds according to any one of embodiments 1) to 7).

[0056] 11) Another embodiment relates to compounds according to any one of embodiments 1) to 10), in which L represents methylene.

[0057] 12) Another embodiment relates to compounds according to any one of embodiments 1) to 10), wherein L represents a direct bond.

[0058] 13) In another embodiment, Ar 2 but, - phenyl, unsubstituted or substituted by 1 or 2 substituents; said substituents being C 1-4 -Alkyl (especially methyl), C 1-3 -fluoroalkyl (especially trifluoromethyl), C 1-3 - phenyl, independently selected from alkoxy (especially methoxy), halogen (especially fluoro or chloro), ethynyl and cyano; or - 5- or 6-membered heteroaryl (in particular furanyl, thiophenyl, pyrrolyl, thiazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl or pyrimidinyl), which 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1 or 2 substituents; 1-4 -Alkyl (especially methyl), -CH2-C 3-6 -Cycloalkyl (especially -CH2-cyclopropyl), C 1-3 -fluoroalkyl (especially trifluoromethyl), C 1-3 - 5- or 6-membered heteroaryl (especially furanyl, thiophenyl, pyrrolyl, thiazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl or pyrimidinyl), independently selected from alkoxy (especially methoxy), halogen (especially fluoro or chloro), morpholin-4-yl and amino; represents; relating to a compound according to any one of embodiments 1) to 12).

[0059] 14) Another embodiment is Ar 2 but: - phenyl, unsubstituted or substituted by 1 or 2 substituents; said substituents being C 1-4 -Alkyl (especially methyl), C 1-3 -fluoroalkyl (especially trifluoromethyl), C 1-3 - phenyl, independently selected from alkoxy (especially methoxy), halogen (especially fluoro or chloro) and cyano; or - 5- or 6-membered heteroaryl (in particular thiophenyl, pyrrolyl, isothiazolyl, pyrazolyl, pyridinyl or pyrimidinyl), , independently unsubstituted or substituted by 1 or 2 substituents; 1-4 -Alkyl (especially methyl), -CH2-C 3-6 -Cycloalkyl (especially -CH2-cyclopropyl), C 1-3 -fluoroalkyl (especially trifluoromethyl), C 1-3- 5- or 6-membered heteroaryl (especially thiophenyl, pyrrolyl, isothiazolyl, pyrazolyl, pyridinyl or pyrimidinyl), independently selected from alkoxy (especially methoxy), halogen (especially fluoro or chloro) and morpholin-4-yl; represents; relating to a compound according to any one of embodiments 1) to 12).

[0060] 15) In another embodiment, Ar 2 but: - phenyl, substituted by 1 or 2 substituents; said substituents being C 1-3 -phenyl, independently selected from fluoroalkyl (especially trifluoromethyl) and halogen; or - 5- or 6-membered heteroaryl (in particular thiophenyl, pyrrolyl, pyrazolyl, pyridinyl or pyrimidinyl), which 5- or 6-membered heteroaryl is independently substituted by 1 or 2 substituents; 1-4 -Alkyl (especially methyl) and C 1-3 - 5- or 6-membered heteroaryl (especially thiophenyl, pyrrolyl, pyrazolyl, pyridinyl or pyrimidinyl), independently selected from fluoroalkyl (especially trifluoromethyl); represents; relating to a compound according to any one of embodiments 1) to 12).

[0061] 16) Another embodiment is the fragment -L-Ar 2 but:

[0062] [ka]

[0063] [ka]

[0064] [ka]

[0065] [ka] with respect to the compound according to any one of embodiments 1) to 10), Each of the above groups A) to H) forms a specific subembodiment; further subembodiments relate to groups A), B) and / or C).

[0066] 17) Another embodiment relates to compounds according to any one of embodiments 1) to 16), in which n represents the integer 1.

[0067] 18) 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 17) 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, 4+1, 5+1, 6+1, 7+1, 8+1, 8+2+1, 8+3+1, 8+4+1, 8+5+1, 8+6+1, 8+7+1, 9+1, 9+2+1, 9+3+1, 9+4+1, 9+5+1, 9+6+1, 9+7+1, 10+1, 10+2+1, 10+3+1, 10+4+1, 10+5+1, 10+6+1, 10+7+1, 11+1, 11+2+1, 11+3+1, 11+4+1, 11+5+1, 11+6+1, 11+7+1, 11+8+1, 11+8+2+1, 11+8+3+1, 11+8+4+1, 11+8+5+1, 11+8+6+1, 11+8+7+1, 11+9+1, 11+9+2+1, 11+9+3+1, 11+9+4+1, 11+9+5+1, 11+9+6+1, 11+9+7+1, 11+10+1, 11+10+2+1, 11+10+3+1, 11+10+4+1 、11+10+5+1、11+10+6+1、11+10+7+1、12+1、12+2+1、12+3+1、12+4+1、12+5+1、12+6+1、12+7+1、12+8+1、12+8+2+1、12+8+3+1、12+8+4+1、12+8+5+1、12+8+6+1、12+8+7+1、12+9+1、12+9+2+1、12+9+3+1、12+9+4+1、12+9+5+1、12+9+6+1、12+9+7+1、12+10+1、12+10+2+1、12+10+3+1、12+10+4+1、12+10+5+1、12+10+6+1、12+10+7+1、13+1、13+2+1、13+3+1、13+4+1、13+5+1、13+6+1、13+7+1、13+8+1、13+8+2+1、13+8+3+1、13+8+4+1、13+8+5+1、13+8+6+1、13+8+7+1、13+9+1、13+9+2+1、13+9+3+1、13+9+4+1、13+9+5+1、13+9+6+1、13+9+7+1、13+10+1、13+10+2+1、13+10+3+1、13+10+4+1、13+10+5+1、13+10+6+1、13+10+7+1、13+11+1、13+11+2+1、13+11+3+1、13+11+4+1、13+11+5+1、13+11+6+1、13+11+7+1、13+11+8+1、13+11+8+2+1、13+11+8+3+1、13+11+8+4+1、13+11+8+5+1、13+11+8+6+1、13+11+8+7+1、13+11+9+1、13+11+9+2+1、13+11+9+3+1、13+11+9+4+1、13+11+9+5+1、13+11+9+6+1、13+11+9+7+1、13+11+10+1、13+11+10+2+1、13+11+10+3+1、13+11+10+4+1、13+11+10+5+1、13+11+10+6+1、13+11+10+7+1、13+12+1、13+12+2+1、13+12+3+1、13+12+4+1、13+12+5+1、13+12+6+1、13+12+7+1、13+12+8+1、13+12+8+2+1、13+12+8+3+1、13+12+8+4+1、13+12+8+5+1、13+12+8+6+1、13+12+8+7+1、13+12+9+1、13+12+9+2+1、13+12+9+3+1、13+12+9+4+1、13+12+9+5+1、13+12+9+6+1、13+12+9+7+1、13+12+10+1、13+12+10+2+1、13+12+10+3+1、13+12+10+4+1、13+12+10+5+1、13+12+10+6+1、13+12+10+7+1、14+1、14+2+1、14+3+1、14+4+1、14+5+1、14+6+1、14+7+1、14+8+1、14+8+2+1、14+8+3+1、14+8+4+1、14+8+5+1、14+8+6+1、14+8+7+1、14+9+1、14+9+2+1、14+9+3+1、14+9+4+1、14+9+5+1、14+9+6+1、14+9+7+1、14+10+1、14+10+2+1、14+10+3+1、14+10+4+1、14+10+5+1、14+10+6+1、14+10+7+1、14+11+1、14+11+2+1、14+11+3+1、14+11+4+1、14+11+5+1、14+11+6+1、14+11+7+1、14+11+8+1、14+11+8+2+1、14+11+8+3+1、14+11+8+4+1、14+11+8+5+1、14+11+8+6+1、14+11+8+7+1、14+11+9+1、14+11+9+2+1、14+11+9+3+1、14+11+9+4+1、14+11+9+5+1、14+11+9+6+1、14+11+9+7+1、14+11+10+1、14+11+10+2+1、14+11+10+3+1、14+11+10+4+1、14+11+10+5+1、14+11+10+6+1、14+11+10+7+1、14+12+1、14+12+2+1、14+12+3+1、14+12+4+1、14+12+5+1、14+12+6+1、14+12+7+1、14+12+8+1、14+12+8+2+1、14+12+8+3+1、14+12+8+4+1、14+12+8+5+1、14+12+8+6+1、14+12+8+7+1、14+12+9+1、14+12+9+2+1、14+12+9+3+1、14+12+9+4+1、14+12+9+5+1、14+12+9+6+1、14+12+9+7+1、14+12+10+1、14+12+10+2+1、14+12+10+3+1、14+12+10+4+1、14+12+10+5+1、 14+12+10+6+1、14+12+10+7+1、15+1、15+2+1、15+3+1、15+4+1、15+5+1、15+6+1、15+7+1、15+8+1、15+8+2+1、15+8+3+1、15+8+4+1、15+8+5+1、15+8+6+1、15+8+7+1、15+9+1、15+9+2+1、15+9+3+1、15+9+4+1、15+9+5+1、15+9+6+1、15+9+7+1、15+10+1、15+10+2+1、15+10+3+1、15+10+4+1、15+10+5+1、15+10+6+1、15+10+7+1、15+11+1、15+11+2+1、15+11+3+1、15+11+4+1、15+11+5+1、15+11+6+1、15+11+7+1、15+11+8+1、15+11+8+2+1、15+11+8+3+1、15+11+8+4+1、15+11+8+5+1、15+11+8+6+1、15+11+8+7+1、15+11+9+1、15+11+9+2+1、15+11+9+3+1、15+11+9+4+1、15+11+9+5+1、15+11+9+6+1、15+11+9+7+1、15+11+10+1、15+11+10+2+1、15+11+10+3+1、15+11+10+4+1、15+11+10+5+1、15+11+10+6+1、15+11+10+7+1、15+12+1、15+12+2+1、15+12+3+1、15+12+4+1、15+12+5+1、15+12+6+1、15+12+7+1、15+12+8+1、15+12+8+2+1、15+12+8+3+1、15+12+8+4+1、15+12+8+5+1、15+12+8+6+1、15+12+8+7+1、15+12+9+1、15+12+9+2+1、15+12+9+3+1、15+12+9+4+1、15+12+9+5+1、15+12+9+6+1、15+12+9+7+1、15+12+10+1、15+12+10+2+1、15+12+10+3+1、15+12+10+4+1、15+12+10+5+1、15+12+10+6+1、15+12+10+7+1、16+1、16+2+1、16+3+1、16+4+1、16+5+1、16+6+1、16+7+1、16+8+1、16+8+2+1、16+8+3+1、16+8+4+1、16+8+5+1、16+8+6+1、16+8+7+1、16+9+1、16+9+2+1、16+9+3+1、16+9+4+1、16+9+5+1、16+9+6+1、16+9+7+1、16+10+1、16+10+2+1、16+10+3+1、16+10+4+1、16+10+5+1、16+10+6+1、16+10+7+1、17+1、17+2+1、17+3+1、17+4+1、17+5+1、17+6+1、17+7+1、17+8+1、17+8+2+1、17+8+3+1、17+8+4+1、17+8+5+1、17+8+6+1、17+8+7+1、17+9+1、17+9+2+1、17+9+3+1、17+9+4+1、17+9+5+1、17+9+6+1、17+9+7+1、17+10+1、17+10+2+1、17+10+3+1、17+10+4+1、17+10+5+1、17+10+6+1、17+10+7+1、17+11+1、17+11+2+1、17+11+3+1、17+11+4+1、17+11+5+1、17+11+6+1、17+11+7+1、17+11+8+1、17+11+8+2+1、17+11+8+3+1、17+11+8+4+1、17+11+8+5+1、17+11+8+6+1、17+11+8+7+1、17+11+9+1、17+11+9+2+1、17+11+9+3+1、17+11+9+4+1、17+11+9+5+1、17+11+9+6+1、17+11+9+7+1、17+11+10+1、17+11+10+2+1、17+11+10+3+1、17+11+10+4+1、17+11+10+5+1、17+11+10+6+1、17+11+10+7+1、17+12+1、17+12+2+1、17+12+3+1、17+12+4+1、17+12+5+1、17+12+6+1、17+12+7+1、17+12+8+1、17+12+8+2+1、17+12+8+3+1、17+12+8+4+1、17+12+8+5+1、17+12+8+6+1、17+12+8+7+1、17+12+9+1、17+12+9+2+1、17+12+9+3+1、17+12+9+4+1、17+12+9+5+1、17+12+9+6+1、17+12+9+7+1、17+12+10+1、17+12+10+2+1、17+12+10+3+1、17+12+10+4+1、17+12+10+5+1、17+12、 +10+6+1、17+12+10+7+1、17+13+1、17+13+2+1、17+13+3+1、17+13+4+1、17+13+5+1、17+13+6+1、17+13+7+1、17+13+8+1、17+13+8+2+1、17+13+8+3+1、17+13+8+4+1、17+13+8+5+1、17+13+8+6+1、17+13+8+7+1、17+13+9+1、17+13+9+2+1、17+13+9+3+1、17+13+9+4+1、17+13+9+5+1、17+13+9+6+1、17+13+9+7+1、17+13+10+1、17+13+10+2+1、17+13+10+3+1、17+13+10+4+1、17+13+10+5+1、17+13+10+6+1、17+13+10+7+1、17+13+11+1、17+13+11+2+1、17+13+11+3+1、17+13+11+4+1、17+13+11+5+1、17+13+11+6+1、17+13+11+7+1、17+13+11+8+1、17+13+11+8+2+1、17+13+11+8+3+1、17+13+11+8+4+1、17+13+11+8+5+1、17+13+11+8+6+1、17+13+11+8+7+1、17+13+11+9+1、17+13+11+9+2+1、17+13+11+9+3+1、17+13+11+9+4+1、17+13+11+9+5+1、17+13+11+9+6+1、17+13+11+9+7+1、17+13+11+10+1、17+13+11+10+2+1、17+13+11+10+3+1、17+13+11+10+4+1、17+13+11+10+5+1、17+13+11+10+6+1、17+13+11+10+7+1、17+13+12+1、17+ 13+12+2+1、17+13+12+3+1、17+13+12+4+1、17+13+12+5+1、17+13+12+6+1、17+13+12+7+1、17+13+12+8+1、17+13+12+8+2+1、17+13+12+8+3+1、17+13+12+8+4+1、17+13+12+8+5+1、17+13+12+8+6+1、17+13+12+8+7+1、17+13+12+9+1、17+13+12+9+2+1、17+13+12+9+3+1、17+13+12+9+4+1、17+13+12+9+5+1、17+13+12+9+6+1、17+13+12+9+7+1、17+13+12+10+1、17+13+12+10+2+1、17+13+12+10+3+1、17+13+12+10+4+1、17+13+12+10+5+1、17+13+12+10+6+1、17+13+12+10+7+1、17+14+1、17+14+2+1、17+14+3+1、17+14+4+1、17+14+5+1、17+14+6+1、17+14+7+1、17+14+8+1、17+14+8+2+1、17+14+8+3+1、17+14+8+4+1、17+14+8+5+1、17+14+8+6+1、17+14+8+7+1、17+14+9+1、17+14+9+2+1、17+14+9+3+1、17+14+9+4+1、17+14+9+5+1、17+14+9+6+1、17+14+9+7+1、17+14+10+1、17+14+10+2+1、17+14+10+3+1、17+14+10+4+1、17+14+10+5+1、17+14+10+6+1、17+14+10+7+1、17+14+11+1、17+14+11+2+1、17+14+11+3+1、17+14+11+4+1、17+14+11+5+1、17+14+11+6+1、17+14+11+7+1、17+14+11+8+1、17+14+11+8+2+1、17+14+11+8+3+1、17+14+11+8+4+1、17+14+11+8+5+1、17+14+11+8+6+1、17+14+11+8+7+1、17+14+11+9+1、17+14+11+9+2+1、17+14+11+9+3+1、17+14+11+9+4+1、17+14+11+9+5+1、17+14+11+9+6+1、17+14+11+9+7+1、17+14+11+10+1、17+14+11+10+2+1、17+14+11+10+3+1、17+14+11+10+4+1、17+14+11+10+5+1、17+14+11+10+6+1、17+14+11+10+7+1、17+、 14+12+1、17+14+12+2+1、17+14+12+3+1、17+14+12+4+1、17+14+12+5+1、17+14+12+6+1、17+14+12+7+1、17+14+12+8+1、17+14+12+8+2+1、17+14+12+8+3+1、17+14+12+8+4+1、17+14+12+8+5+1、17+14+12+8+6+1、17+14+12+8+7+1、17+14+12+9+1、17+14+12+9+2+1、17+14+12+9+3+1、17+14+12+9+4+1、17+14+12+9+5+1、17+14+12+9+6+1、17+14+12+9+7+1、17+14+12+10+1、17+14+12+10+2+1、17+14+12+10+3+1、17+14+12+10+4+1、17+14+12+10+5+1、17+14+12+10+6+1、17+14+12+10+7+1、17+15+1、17+15+2+1、17+15+3+1、17+15+4+1、17+15+5+1、17+15+6+1、17+15+7+1、17+15+8+1、17+15+8+2+1、17+15+8+3+1、17+15+8+4+1、17+15+8+5+1、17+15+8+6+1、17+15+8+7+1、17+15+9+1、17+15+9+2+1、17+15+9+3+1、17+15+9+4+1、17+15+9+5+1、17+15+9+6+1、17+15+9+7+1、17+15+10+1、17+15+10+2+1、17+15+10+3+1、17+15+10+4+1、17+15+10+5+1、17+15+10+6+1、17+15+10+7+1、17+15+11+1、17+15+11+2+1、17+15+11+3+1、17+15+11+4+1、17+15+11+5+1、17+15+11+6+1、17+15+11+7+1、17+15+11+8+1、17+15+11+8+2+1、17+15+11+8+3+1、17+15+11+8+4+1、17+15+11+8+5+1、17+15+11+8+6+1、17+15+11+8+7+1、17+15+11+9+1、17+15+11+9+2+1、17+15+11+9+3+1、17+15+11+9+4+1、17+15+11+9+5+1、17+15+11+9+6+1, 17+15+11+9+7+1, 17+15+11+10+1, 17+15+11+10+2+1, 17+15+11+10+3+1, 17+15+11+10+4+1, 17+15+11+10+5+1, 17+15+11+10+6+1, 17+15+11+10+7+1, 17+15+12+1, 17+15+12+2+1, 17+15+12+3+1, 17+15+12+4+1, 17+15+12+5+1, 17+15+12+6+1, 17+15+12+7+1, 17+15+12+8+1, 17+15+12+8+2+1, 17+15+12+8+3+1, 17+15+12+8+4+1, 17+15+12+8+5+1, 17+15+12+8+6+1, 17+15+12+8+7+1, 17+15+12+9+1, 17+15+12+9+2+1, 17+15+12+9+3+1, 17+15+12+9+4+1, 17+15+12+9+5+1, 17+15+12+9+6+1, 17+15+12+9+7+ 1, 17+15+12+10+1, 17+15+12+10+2+1, 17+15+12+10+3+1, 17+15+12+10+4+1, 17+15+12+10+5+1, 17+15+12+10+6+1, 17+15+12+10+7+1, 17+16+1, 17+16+2+1, 17+16+3+1, 17+16+4+1, 17+16+5+1, 17+16+6+1, 17+16+7+1, 17+16+8+1, 17+16+8+2+1, 17+16+8+3+1, 17 +16+8+4+1, 17+16+8+5+1, 17+16+8+6+1, 17+16+8+7+1, 17+16+9+1, 17+16+9+2+1, 17+16+9+3+1, 17+16+9+4+1, 17+16+9+5+1, 17+16+9+6+1, 17+16+9+7+1, 17+16+10+1, 17+16+10+2+1, 17+16+10+3+1, 17+16+10+4+1, 17+16+10+5+1, 17+16+10+6+1, 17+16+10+7+1.

[0068] In the above list, the numbers refer to the embodiment according to the number and "+" indicates a dependency from another embodiment. The various embodiments are individually separated by commas. In other words, for example, "1 "7+16+7+1" means embodiment 17) which is dependent on embodiment 16) which is dependent on embodiment 7) which is dependent on embodiment 1), i.e. embodiment "17+16+7+1" corresponds to compounds of formula (I) according to embodiment 1) further limited by all the features of embodiments 7), 16) and 17).

[0069] 19) Another embodiment relates to compounds of formula (I) according to embodiment 1), which are selected from the following compounds: (2R,3R,4S,5R,6R)-N-benzyl-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorobenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-ethynylbenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-phenethyl-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(4-chlorobenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2-chlorobenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3-chloropyridin-4-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((2-(trifluoromethyl)pyridin-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((4-(trifluoromethyl)pyridin-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-(trifluoromethyl)benzyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2-chlorobenzyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((3-(trifluoromethyl)pyridin-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((2-methyl-1H-imidazol-4-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((2-amino-4-chlorothiazol-5-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(isoxazol-4-ylmethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((5-chlorofuran-2-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide;(2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(isothiazol-4-ylmethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-imidazol-4-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((2-bromothiazol-4-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((2-morpholinothiazol-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carbo oxamide; (2R,3R,4S,5R,6R)-N-((5-chlorothiophen-2-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((5-chlorothiazol-2-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-pyrazol-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((3-(trifluoromethyl)pyridin-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((2-(trifluoromethyl)pyridin-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((4-(trifluoromethyl)pyrimidin-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((4,6-dimethoxypyrimidin-5-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((4-methylpyrimidin-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((5-methyl-1H-imidazol-4-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((4-chloroisothiazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2- Carboxamides; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-pyrazol-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((3-methylthiophen-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-pyrrol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3-chlorothiophen-2-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((4-methylthiazol-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-imidazol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((2-methylthiophen-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-methoxybenzyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2,6-dimethoxybenzyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-imidazol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2 -hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-imidazol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-((1-ethyl-1H-pyrazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-isopropyl-1H-pyrazol-5-yl)methyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((1-(cyclopropylmethyl)-1H-pyrazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-indol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3-chlorobenzyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; and (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide.

[0070] 20) In addition to the compounds described in embodiment 19), further compounds according to embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-((6-fluoro-3-methoxyquinoxalin-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3-chloroquinolin-2-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carbo oxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-methoxyphenyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluoro-2-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(5-fluoro-2-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide D; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-methoxyphenyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyanophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(methoxy-d3)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide ; (2R,3R,4S,5R,6R)-N-(5-chloro-2-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-4-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-4-(trifluoromethyl)phenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-4-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-methylbenzo[d]thiazol-6-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-(trifluoromethyl)phenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,4-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-4-chlorophenyl)-5-phenyl Droxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-phenyl-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-methoxyphenyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[b]thiophen-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(5-chloro-2-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2,5-dimethylbenzo[d]thiazol-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2-chlorobenzo[d]thiazol-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(5-bromo-2-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide ; (2R,3R,4S,5R,6R)-N-(4-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-(trifluoromethyl)phenyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-fluoro-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-fluoro-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H- 1,2,3-Triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(m-tolyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-methyl-1H-benzo[d]imidazol-6-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-6-yl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-fluorophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-5-yl)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl (1S,2S)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-fluorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-6-yl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; 2-(((2R,3R,4S,5R,6R)-2-((3-chloro-5-cyanophenyl)((1S,2S)-2-hydroxycyclohexyl)carbamoyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)oxy)acetic acid; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-morpholino-2-oxoethoxy)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4,5-difluoro-2-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluoro-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(2-methylbenzo[d]thiazol-6-yl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(4-fluoronaphthalen-1-yl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl)-N-(2,3-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(pyridin-2-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(naphthalen-2-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(naphthalen-1-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(1,5-dimethyl-1H-pyrazol-3-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl) nyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycycloheptyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycycloheptyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-morpholino-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-((S)-3-hydroxypyrrolidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-((R)-3-hydroxypyrrolidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-(4-hydroxypiperidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-3-(2-(3-hydroxyazetidin-1-yl)-2-oxoethoxy)-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; 2-(((2R,3R,4S,5R,6R)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclohexyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl)oxy)acetic acid; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxylate Ruboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-morpholinophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; and (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-((3-hydroxypropyl)amino)phenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide.

[0071] The compounds of formula (I) according to embodiments 1) to 20) 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.

[0072] 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.

[0073] 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 20). In a subembodiment of the invention, the dosage is comprised between 1 mg and 1000 mg per day.

[0074] 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.

[0075] 21) Another embodiment relates to compounds of formula (I) as defined in any one of embodiments 1) to 20), useful for the prevention or treatment of diseases and disorders in which the binding of galectin-3 to its natural ligand is involved.

[0076] 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.

[0077] 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, especially idiopathic pulmonary fibrosis (also called cryptogenic fibrosing alveolitis); rheumatoid arthritis, scleroderma (systemic sclerosis, SSc), lupus (systemic lupus erythematosus, all forms of lung / pulmonary fibrosis, including pulmonary fibrosis secondary to systemic inflammatory diseases such as systemic lupus erythematosus (SLE), polymyositis, or mixed connective tissue disease (MCTD); pulmonary fibrosis secondary to sarcoidosis; iatrogenic pulmonary fibrosis, including radiation-induced fibrosis; silicosis-induced pulmonary fibrosis; asbestos-induced pulmonary fibrosis; and pleural fibrosis; -- renal / kidney fibrosis, including chronic kidney disease (CKD), renal failure (acute or chronic), tubulointerstitial nephritis and / or chronic nephropathy such as (primary) glomerulonephritis and glomerulonephritis secondary to systemic inflammatory diseases such as SLE and SSc, diabetes, focal segmental glomerulosclerosis, IgA nephropathy, hypertension, renal transplantation and renal fibrosis due to / associated with Alport syndrome; -- all forms of liver / hepatic fibrosis (whether or not associated with portal hypertension), including cirrhosis, alcohol-induced liver fibrosis, non-alcoholic steatohepatitis, bile duct injury, primary biliary cirrhosis (also known as primary biliary cholangitis), infectious or virally induced liver fibrosis (e.g. chronic HCV infection) and autoimmune hepatitis; -- Cardiovascular disease, heart failure, Fabry disease, CKD; 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 mellitus 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 (such as stones, prostatic hyperplasia, prostate cancer, retroperitoneal pelvic tumors, etc.), Acute kidney injury and chronic kidney disease (CKD) caused by / associated with obstructive nephropathy (including uremic pelvic tumors) or caused by / associated with neurogenic bladder disease-related symptoms (particularly CKD stages 1 to 5 as defined in the Kidney Disease Improving Global Outcomes (KDIGO) Guidelines), 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.

[0078] 22) A further embodiment relates to a compound of formula (I) for use according to embodiment 21), 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.

[0079] 23) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein said compounds are for use in the prevention or treatment of cardiovascular diseases and disorders.

[0080] 24) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein the compounds are for use in the prevention or treatment of acute kidney injury and chronic kidney disease (CKD).

[0081] 25) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein the compounds are for use in the prevention or treatment of (acute or chronic) liver diseases and disorders.

[0082] 26) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein the compounds are for use in the prevention or treatment of interstitial lung diseases and disorders.

[0083] 27) A further embodiment relates to a compound of formula (I) for use according to embodiment 21), wherein the compound is for use in the prevention or treatment of eye diseases and disorders.

[0084] 28) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein the compounds are for use in the prevention or treatment of cell proliferative disorders and cancer.

[0085] 29) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein the compounds are for use in the prevention or treatment of chronic and acute inflammatory and autoimmune diseases and disorders.

[0086] 30) A further embodiment relates to a compound of formula (I) for use according to embodiment 21), wherein the compound is for use in the prevention or treatment of gastrointestinal diseases and disorders.

[0087] 31) A further embodiment relates to a compound of formula (I) for use according to embodiment 21), wherein the compound is for use in the prevention or treatment of pancreatic diseases and disorders.

[0088] 32) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein the compounds are for use in the prevention or treatment of diseases and disorders associated with abnormal angiogenesis.

[0089] 33) A further embodiment relates to a compound of formula (I) for use according to embodiment 21), wherein the compound is for use in the prevention or treatment of brain-related diseases and disorders.

[0090] 34) A further embodiment relates to compounds of formula (I) for use according to embodiment 21), wherein the compounds are for use in the prevention or treatment of neuropathic pain and peripheral neuropathy.

[0091] 35) A further embodiment relates to a compound of formula (I) for use according to embodiment 21), wherein the compound is for use in the treatment of transplant rejection.

[0092] 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 by-products. In the general reaction sequences outlined below, the integer n and the generic group, R 1 , L, Ar 1 and Ar 2 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 , L, Ar 1 and Ar 2 may not be compatible with the preparation illustrated in the scheme below and would require the use of a protecting group (Pg). The use of protecting groups is well known in the art (see, for example, "Protective Groups in Organic Synthesis", TW Greene, PG M Huts, Wiley-Interscience, 1999). For this purpose, it is assumed that such protecting groups have been introduced as necessary. In some cases, the final product may be further modified, for example by manipulating the substituents to give new final products. Such manipulations include, but are not limited to, reduction, oxidation, alkylation, acylation, hydrolysis and transition metal catalyzed cross-coupling reactions well known to those skilled in the art. The resulting compounds may be converted into salts, particularly pharma- ceutically acceptable salts, by methods known in the art.

[0093] 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.

[0094] The compounds of formula (I) may be prepared by reacting R with H, a suitable protecting group (Pg) or R 1 The compound of Structure 1, which is: is coupled with the compound of Structure 2 to give Structure 3. The coupling reaction is carried out using standard peptide coupling conditions such as DCC, HOBT or T3P in a suitable solvent such as DCM or DMF or mixtures thereof in the presence of a base such as TEA or DIPEA. Alternatively, POCl3 can be used with pyridine as the base. In Structures 2 and 3, Pg is a suitable protecting group such as acetyl, trimethylsilyl (TMS) or tert-butyl dimethylsilyl (TBS) or benzyl, which are well known to those skilled in the art. The hydroxy groups at positions 4 and 6 of Structure 1 can be protected with cyclic protecting groups such as isopropylidene, benzylidene or bis-tert-butylsilyl groups. R is hydrogen, a suitable protecting group (Pg) or R (as defined in formula (I)). 1 The compound of structure 3 is then deprotected to give the compound of formula (I).

[0095] [ka] In the case where Pg represents an acyl protecting group, such protecting groups can be cleaved under standard conditions, for example with water or alcohols in the presence or absence of additional solvents such as THF, dioxane, and in the presence of bases such as K2CO3, NaOH, LiOH. In the case where such protecting groups represent benzyl groups, they can be cleaved, for example, with hydrogen in the presence of catalysts such as Pd / C, PtO2, in methanol, EA, THF, etc. or mixtures thereof, or with BBr3 in a solvent such as DCM. In the case where such protecting groups are TMS or TBS, they are cleaved with fluoride ions such as TBAF or HF in pyridine. Alternatively, silyl protecting groups are removed under mild acidic conditions, such as aqueous acetic acid, at temperatures between rt and reflux. In the case where Pg represents a cyclic protecting group, such as isopropylidene, benzylidene and bis-tert-butylsilylene groups, the cleavage can be carried out under acidic conditions using aqueous acetic acid or TFA.

[0096] [ka] Compounds of structure 1 are prepared by hydrolysis of the nitrile functionality in structure 4 to a carboxylic acid using aqueous acidic (conc. HCl) or basic (NaOH) conditions at temperatures between 20 and 100° C., followed by appropriate protection or modification of the free hydroxyl group. Alternatively, structure 4 can be obtained by reacting compounds of structure 5 with compounds of structure 6 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 6 are commercially available or can be prepared according to procedures known to those skilled in the art (Synthesis 2011, 22, 3604-3611). Structure Compound 5 can be prepared from the corresponding gulo furanose derivative by methods well known to those skilled in the art (Carbohydrate Research 1994, 251, 33-67; Bioorg. Med. Chem. 2002, 10, 1911-2013).

[0097] [ka] Compounds of structure 2 can be obtained by protecting compounds of structure 7 with a suitable silyl-based protecting group under standard conditions. Compounds of structure 7 can be obtained, for example, by functionalizing (1S,2S)-trans-2-aminocyclohexanol or (1S,2S)-trans-2-aminocycloheptanol by reductive amination using a suitable carbonyl component and a reducing agent such as NaB(OAc)3H or NaCNBH3 in a suitable solvent such as DCM, MeOH, THF, DMF or mixtures thereof. Alternatively, compounds of structure 7 can be obtained by reaction of cyclohexene oxide or cycloheptane oxide with amines. This reaction can be carried out with a racemic trans-amino alcohol or with a suitable catalyst as reported in Org.Lett. 2014, 16, 2798-2801 to produce enantiomerically enriched derivatives. When a compound of structure 7 is used in racemic form, the diastereomers of structure 3 or formula 1 can be separated after coupling with a compound of structure 1 using techniques well known to those skilled in the art, such as chiral preparative HPLC or SiO2 column chromatography.

[0098] Whenever the compound of formula (I) is obtained in the form of a mixture of stereoisomers, the stereoisomers can be separated by preparative HPLC using achiral or chiral stationary phases such as Waters XBridge C18, 10 μm OBD, 30x75 mm, or Daicel ChiralCel OJ-H (5-10 μm) columns, Daicel ChiralPak IH (5 μm) or AS-H (5 μm) or IB (5 μm) columns, respectively. 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.

[0099] Experimental section The following examples illustrate the invention but do not in any way limit its scope.

[0100] All temperatures are given in °C. Commercially available starting materials were used as received without further purification. All reactions were carried out under a nitrogen or argon atmosphere unless otherwise noted. Compounds were purified by flash chromatography on silica gel (Biotage) using preparative TLC (Merck TLC plates, Silica gel 60 F 254 ) or by preparative HPLC. The compounds described in this invention were 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 = broadband; coupling constants are given in Hz.) and / or LC-MS (retention time t R are given in min; molecular weights obtained from mass spectrometry are given in g / mol.) using the conditions described below.

[0101] Qualitative analysis methods used LC-MS retention times were obtained using the following elution conditions: A) LC-MS(A): Zorbax RRHD SB-Aq, 1.8 m, 2.1x50 mm column, thermostated at 40°C. The two elution solvents were: 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 eluted mixture related to the time t from the start of the elution are summarized in the table below (a linear gradient is used between two successive time points):

[0102] [Table 1] B) LC-MS(B): Waters BEH C18, 1.8 m, 1.2x50 mm column, thermostated at 40°C. The two elution solvents were: Solvent A = water + 13 mM NH4OH; Solvent B = acetonitrile. The eluent flow rate was 0.8 mL / min and the characteristics of the proportion of the eluted mixture related to the time t from the start of the elution are summarized in the table below (a linear gradient is used between two successive time points):

[0103] [Table 2] D) LC-MS(D): Waters Acquity UPLC CSH C18 1.7 μm, 2.1×50 mm column, thermostated at 60° C. The two elution solvents were: Solvent A=water+0.05% formic acid; Solvent B=acetonitrile. The eluent flow rate was 1 mL / min and the characteristics of the proportion of the eluted mixture related to the time t from the start of the elution are summarized in the table below (a linear gradient is used between two successive time points):

[0104] [Table 3] E) LC-MS(E): Waters Acquity UPLC CSH C18 1.7 μm, 2.1x50 mm column, thermostated at 60° C. The two elution solvents were: Solvent A=water + 0.05% formic acid; Solvent B=acetonitrile + 0.045% formic acid. The eluent flow rate was 1 mL / min and the characteristics of the elution mixture proportions related to the time t from the start of the elution are shown in the table below. To summarize (using a linear slope between two consecutive time points):

[0105] [Table 4] Purification by preparative LC-MS was carried out using the conditions described below. C) Preparative LC-MS(I): A Waters column (Waters XBridge C18, 10 μm OBD, 30×75 mm) was used. The two elution solvents were: Solvent A=water+0.5% of 25% NH4OH in water; Solvent B=acetonitrile. The eluent flow rate was 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):

[0106] [Table 5] Abbreviations (as used herein): ABTS 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid AcOH Acetic acid aq. aqueous solution Bu (in nBuLi = n-butyl lithium, etc.) Ca approx. CC Silica Column Chromatography Concentrated CSA 10-camphor-sulfonic acid 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 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 Hept Heptane HOBt 1-Hydroxybenzotriazole hydrate HPLC High Performance Liquid Chromatography hv high vacuum LAH Lithium Aluminum Hydride LDA Lithium diisopropylamide LC Liquid Chromatography M Molar concentration [mol L -1 ] Me Methyl MeCN Acetonitrile MeOH Methanol MS mass spectrometry min. N normality NaOMe Sodium methoxide NaOtBu Sodium tert.(tertiary)butoxide 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 TBME tert-Butyl methyl ether TBTU O-Benzotriazol-1-yl-N,N,N',N'-tetramethyluronium tetrafluoroborate tBu tert-butyl = tertiary butyl TEA Triethylamine Tf Trifluoromethanesulfonate TFA Trifluoroacetic acid THF Tetrahydrofuran TMS Trimethylsilyl T3P Propylphosphonic anhydride t R retention time A. Preparation of precursors and intermediates The following precursors were prepared for the synthesis of the compounds:

[0107] [ka] Intermediate 1: (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate is synthesized from (3aR,5S,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol according to the literature procedure from Ref: Carbohydrate Research 1994, 251, 33-67 and references cited therein.

[0108] Intermediate 2: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Intermediate 1 (10000 mg, 26.5 mmol, 1 eq) is dissolved in nitromethane (4 vol.) (40 mL) and trimethylsilyl cyanide 98% (10.2 mL, 79.6 mmol, 3 eq) and boron trifluoride diethyl etherate (3.93 mL, 31.8 mmol, 1.2 eq) are added in portions over 30 min. The temperature is kept below 35° C. with a water bath. The mixture is stirred at rt for 2 h. The mixture is partitioned between water (400 mL), sat. aq. bicarbonate (100 mL) and TBME (300 mL). The aqueous phase is extracted once more with TBME (200 mL) and the organic phase is washed twice with water / brine (ca. 5:1) and brine and dried over MgSO4. TBME is evaporated on a Rotavap at 20° C. The crude intermediate is purified by filtration over SiO2 (150 mL cartridge 3 / 4 packed, DCM / TBME 10:1). The intermediate is used immediately in the next step. 1H NMR (500 MHz, DMSO) δ: 5.47 (dd, J 1 = 0.7Hz, J 2 =3.2Hz, 1H), 5.17(t, J=10.3Hz, 1H), 5.04(d, J=10.1Hz, 1H), 4.22(dd, J 1 = 3.2Hz, J 2 =10.4Hz, 1H), 4.15(ddd, J 1 =0.8Hz, J 2 = 4.5Hz, J 3 =7.2Hz, 1H), 4.03-4.08(m, 1H), 3.97(dd, J 1 = 7.4Hz, J 2 =11.7Hz, 1H), 2.18(s, 3H), 2.15(m, 3H), 2.04(s, 3H).

[0109] Intermediate 3a: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Intermediate 2 is dissolved in DMF (80 mL) and 5-ethynyl-1,2,3-trifluorobenzene (312 mg, 21.2 mmol, 0.8 eq), DIPEA (13.6 mL, 79.6 mmol, 3 eq) and CuI (505 mg, 2.65 mmol, 0.1 eq) are added under N2. The yellow mixture is stirred at rt for 1 h. Exotherm. The yellow solution is slowly poured into water (800 mL) and stirred for 10 min. The beige precipitate is filtered and the filtrate is discarded. The beige solid is washed with MeOH, then dissolved in EA (300 mL) and stirred for 10 min. The fine Cu residue is filtered and the filtrate is washed with NH4Cl solution (half saturated) and brine, dried over MgSO4 and concentrated. The residue is triturated with MeOH (ca 100 mL), filtered and dried under hv to give the desired intermediate 3a as a beige solid. 1 H NMR (500MHz, DMSO-d6) δ:8.85(s, 1H), 7.81-7.85(m, 2H), 5.91(m, 1H), 5.64(dd, J1=3.1Hz, J2=11.0Hz, 1H), 5.51(dd, J1=0.7Hz, J2=3 .0Hz, 1H), 5.24(d, J=9.9Hz, 1H), 4.43-4.46(m, 1H), 4.03-4.12(m, 2H), 2.10(s, 3H), 2.04(m, 3H), 1.94(m, 3H). LCMS(A):t R =0.86min;[M+H] + =577.28.

[0110] Intermediate 3b: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Prepared analogously to intermediate 3a using the appropriate alkyne derivative (commercially available). LCMS (A): t R =0.95min;[M+H]+=479.23.

[0111] Intermediate 3c: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-cyanotetrahydro-2H-pyran-3,5-diyl diacetate. Prepared analogously to Intermediate 3a using the appropriate alkyne derivative (commercially available). LCMS (A):t R = 1.00min;[M+H]+ = 513.28.

[0112] Intermediate 3d: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Prepared analogously to intermediate 3a using the appropriate alkyne derivative (commercially available). LCMS (A):t R = 0.98min;[M+H]+ = 493.26.

[0113] Intermediate 3e: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Prepared analogously to intermediate 3a using the appropriate alkyne derivative (commercially available). LCMS (A): t R =0.91min;[M+H]+=461.18.

[0114] Intermediate 3 is further functionalized as shown in the scheme below.

[0115] [ka] Intermediate 4a: (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxylic acid Intermediate 3a (2800 mg, 5.64 mmol, 1 eq) is suspended in HCl 25% (20.6 mL, 169 mmol, 30 eq) and heated under reflux for 1.5 h. The solution is poured onto a MCI® gel column (ca 100 mL gel) containing water. The column is eluted with water until neutral pH (5 fractions of 40 mL). The compound is then eluted with HO / MeCl2. Elute with N (3:1). Take 40 mL fractions. The product-containing fractions are first concentrated under vacuum to remove MeCN and then lyophilized to give the title compound as a colorless solid. LCMS (A): R = 0.59min;[M+H]+ = 390.22. 1 H NMR (500MHz, DMSO-d6) δ:12.88-12.90(br, 1H), 8.79(s, 1H), 7.86(dd, J 1 = 6.8Hz, J 2 =9.1Hz, 2H), 5.43-5.46(m, 1H), 5.30(d, J=6.2Hz, 1H), 4.84(dd, J 1 = 3.0Hz, J 2 =10.8Hz, 1H), 4.72(d, J=0.5Hz, 1H), 4.36(t, J=10.0Hz, 1H), 3.94(dd, J 1 = 3.0Hz, J 2 =6.0Hz, 1H), 3.85(d, J=9.4Hz, 1H), 3.71(t, J=6.5Hz, 1H), 3.48-3.55(m, 2H).

[0116] Intermediate 4b: (2R,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-carboxylic acid Prepared similarly to intermediate 4a. LCMS(A):t R =0.55min;[M+H]+=371.90.

[0117] Intermediate 4c: (2R,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-carboxylic acid Prepared similarly to intermediate 4a. LCMS(A):t R =0.64min;[M+H]+=406.20.

[0118] Intermediate 4d: (2R,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-carboxylic acid Prepared similarly to intermediate 4a. LCMS(A):t R =0.61min;[M+H]+=386.17.

[0119] Intermediate 4e: (2R,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxylic acid Prepared similarly to intermediate 4a. LCMS(A):t R =0.50min;[M+H]+=354.11.

[0120] Intermediate 5a: (4aR,6R,7R,8R)-7-Hydroxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Intermediate 4a (1780 mg, 4.57 mmol, 1 eq) is dissolved in THF (80 mL) and 2,2-dimethoxypropane (1.17 mL, 9.14 mmol, 2 eq) is added followed by PTSA monohydrate (16.1 mg, 0.0914 mmol, 0.02 eq) at rt.

[0121] The mixture is heated to 75° C. for 1.5 h and 20-25 mL of solvent is evaporated using a Dean-Stark. The solution is cooled to rt, then diluted with EA and washed with 10% citric acid solution, water and brine. The organic layer is dried over MgSO4, filtered and concentrated under reduced pressure to give the title intermediate as a beige solid. LCMS (A): t R =0.8min;[M+H]+=430.20.1H NMR(500MHz, DMSO) δ:12.85-13.10(m, 1H), 8.67(s, 1H), 7.88(dd, J 1 = 9.1Hz, J 2 =6.8Hz, 2H), 5.45-5.59(m, 1H), 4.98(dd, J 1 =10.7 Hz, J 2 =3.4Hz, 1H), 4.32-4.38(m, 2H), 4.01-4.03(m, 1H), 3.94(d, J=9.3Hz, 1H), 3.71-3.76(m, 2H), 1.32(s, 3H), 1.21(s, 3H).

[0122] Intermediate 5b: (4aR,6R,7R,8R,8aR)-8-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-7-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid. Prepared similarly to intermediate 5a. LCMS (A): t R= 0.76min; [M+H] + =412.29.

[0123] Intermediate 5c: (4aR,6R,7R,8R,8aR)-8-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-7-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Prepared similarly to intermediate 5a. LCMS(A):t R =0.84min;[M+H]+=446.24.

[0124] Intermediate 5d: (4aR,6R,7R,8R,8aR)-8-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-7-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Prepared similarly to intermediate 5a. LCMS(A):t R =0.81min;[M+H]+=426.27.

[0125] Intermediate 5e: (4aR,6R,7R,8R,8aR)-8-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-7-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Prepared similarly to intermediate 5a. LCMS(A):t R = 0.72min;[M+H]+ = 394.19.

[0126] Intermediate 6a: (4aR,6R,7R,8R,8aR)-7-Methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Step 1: Methyl (4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylate A solution of intermediate 5a (3180 mg, 7.41 mmol, 1 eq) in DMF (dry) (14.8 mL) and THF (dry) (29.6 mL) was cooled to 0° C. and diluted with dimethyl sulfate. *99.8% (1.44 mL, 15.2 mmol, 2.05 eq) followed by NaH (55% dispersion in mineral oil) (622 mg, 15.6 mmol, 2.1 eq) are added. The mixture is stirred at 0° C. for 30 min and then at rt for 3 h. The mixture is cooled again to 0° C. and quenched by adding saturated NH4Cl solution. The mixture is diluted with water and EA and the layers are separated. The organic layer is washed with water and brine and the aqueous layer is re-extracted once with EA. The organic layers are combined, dried over magnesium sulfate, filtered and evaporated. The residue is precipitated from TBME / Hept and the colourless solid is filtered, washed with a small amount of TBME and dried under hv. The desired methyl ester is isolated as a colourless solid. LCMS (A): t R =0.98min;[M+H]+=458.22. * The same product can also be obtained using iodomethane as a reagent.

[0127] Step 2: (4aR,6R,7R,8R,8aR)-7-Methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid The intermediate from step 1 (1546 mg, 3.38 mmol, 1 eq) is dissolved in THF / MeOH / HO 3:2:1 (34.1 mL) and lithium hydroxide monohydrate (217 mg, 5.07 mmol, 1.5 eq) is added at rt.

[0128] The mixture is stirred at rt for 4 h. The mixture is diluted with water, acidified with 0.1N HCl and extracted twice with EA. The organic layers are washed with brine, combined, dried over magnesium sulfate, filtered and concentrated. The residue is triturated in TBME. The white solid is filtered, washed with TBME and dried under hv to give the desired intermediate as a colorless solid. LCMS (A):t R =0.87min;[M+H]+=444.25.

[0129] Intermediate 6b: (4aR,6R,7R,8S,8aR)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)-7-((trimethylsilyl)oxy)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid To a solution of intermediate 5a (2000 mg, 4.66 mmol, 1 eq) and 2,6-lutidine (0.192 mL, 1.63 mmol, 3.5 eq) in dry DCM (5 mL) is added trimethylsilyl trifluoromethanesulfonate (0.255 mL, 1.4 mmol, 3 eq) dropwise at 0° C. The mixture is stirred at 0° C. for 4.5 h. 2,6-lutidine (1.09 mL, 9.32 mmol, 2 eq) and trimethylsilyl trifluoromethanesulfonate (1.69 mL, 9.32 mmol, 2 eq) are added again at 0° C. and stirring is continued at 0° C. 2,6-Lutidine (1.09 mL, 9.32 mmol, 2 eq) and trimethylsilyl trifluoromethanesulfonate (0.506 mL, 2.79 mmol, 0.6 eq) are added again and stirring is continued for 1 h. The mixture is diluted with DCM and quenched with water at 0 °C. The layers are separated and the organic layer is washed with water and brine. The organic layer is filtered through a phase separator and evaporated. The crude is dried under high pressure and used without purification due to instability.

[0130] Intermediate 6c: (4aR,6R,7R,8S,8aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid To a solution of intermediate 5a (50 mg, 0.116 mmol, 1 eq) in dry DCM (1 mL) under N2 at 0 °C, 2,6-lutidine (0.0274 mL, 0.233 mmol, 2 eq) is added followed by tert-butyldimethylsilyl trifluoromethanesulfonate (0.03 mL, 0.128 mmol, 1.1 eq). The orange solution is then stirred at 0 °C for 1.5 h. The mixture is stirred o / n at rt. tert-butyldimethylsilyl trifluoromethanesulfonate (0.0267 mL, 0.116 mmol, 1 eq) and 2,6-lutidine (0.0271 mL, 0.233 mmol, 2 eq) are added again at 0 °C and the mixture is stirred at 0 °C for 1 h. The mixture is quenched with 10% citric acid and extracted twice with DCM. The organic layers are combined, dried using a phase separator and then concentrated under reduced pressure. The mixture is dissolved in MeCN / water 1 / 1 (1 mL) and treated with HCOOH (0.5 mL). The suspension is stirred at rt for 1 h and then filtered. The solid is purified by FC using a CombiFlash (4 g SiO2 column; gradient: hept to hept / EA 1 / 2 in 15 min) to give the desired product as a colorless solid. LCMS (A):t R = 1.07min;[M+H]+ = 544.30.

[0131] Intermediate 6d: (4aR,6R,7R,8S,8aR)-7-acetoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid To a solution of intermediate 5a (500 mg, 1.16 mmol, 1 eq) in DCM (11.6 mL) and TEA (0.648 mL, 4.66 mmol, 4 eq) is added Ac2O (0.22 mL, 2.33 mmol, 2 eq) followed by DMAP (14.2 mg, 0.116 mmol, 0.1 eq). The mixture is stirred o / n at rt. The mixture is diluted with water and DCM. The pH is carefully adjusted to 5-6 with 10% citric acid and the layers are separated. The aqueous layer is re-extracted once with DCM and the organic layers are combined, dried over MgSO4, filtered and evaporated. The residue is precipitated from TBME / hept+small amount of MeOH. The colorless solid is filtered and washed with TBME to give the desired intermediate as a colorless solid. LCMS (A):t R =0.87min;[M+H]+=472.11.

[0132] Intermediate 6e: (4aR,6R,7R,8S,8aR)-7-acetoxy-8-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid. Prepared similarly to intermediate 6d from 5b. LCMS (A): t R =0.83min;[M+H]+=454.01.

[0133] Intermediate 6f: (4aR,6R,7R,8S,8aR)-7-acetoxy-8-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Prepared from 5c similarly to intermediate 6d. LCMS(A):t R = 0.90min;[M+H]+ = 487.96.

[0134] Intermediate 6g: (4aR,6R,7R,8S,8aR)-7-acetoxy-8-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Prepared from 5d in the same manner as intermediate 6d. LCMS(A):t R =0.88min;[M+H]+=468.09.

[0135] Intermediate 6h: (4aR,6R,7R,8S,8aR)-7-acetoxy-8-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Prepared from 5e similarly to intermediate 6d. LCMS(A):t R =0.79min;[M+H]+=436.04.

[0136] Intermediate 7a: (2R,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-carboxylic acid To a suspension of intermediate 4a (1500 mg, 3.85 mmol, 1 eq) in Ac2O (2.04 mL, 21.2 mmol, 5.5 eq) is added a 70% aqueous solution of perchloric acid (0.00831 mL, 0.0963 mmol, 0.025 eq) at 0 °C. The mixture is stirred at 0 °C for 5 min, then warmed to rt and stirred o / n. The mixture is cooled to 0 °C and diluted with water (50 mL) and THF (5 mL). The mixture is warmed to rt (26 °C, hydrolysis exotherm).

[0137] The mixture is cooled to 0-5°C and the precipitated product is filtered, washed with water and dried under HV o / n to give the product as a white solid. LCMS (A): R =0.85min;[M+H]+=516.13. 1 H NMR (500MHz, DMSO-d6) δ:13.38(d, 1H), 8.84(s, 1H), 7.70-7.95(m, 2H), 5.73(dd, J 1 =11.0Hz, J 2 =9.5Hz), 5.67(dd, J 1 =11.1Hz, J 2=3.2Hz), 5.42-5.45(m, 1H), 4.37-4.42(m, 1H), 4.36(d, J=9.5Hz, 1H), 4.08(dd, J 1 =11.5Hz, J 2 =5.6Hz, 1H), 4.04(dd, J 1 =11.5Hz, J 2 =7.0Hz, 1H), 2.08(s, 3H), 2.01(s, 3H), 1.82(s, 3H).

[0138] Intermediate 8a: (2S,4aR,6R,7R,8R,8aR)-7-Hydroxy-2-phenyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Intermediate 4a (1 g, 2.57 mmol) is dissolved in MeCN (50 mL). Benzaldehyde dimethyl acetal (1 mL) is added followed by PTSA (0.035 g, 0.07 eq). The mixture is stirred at rt for 16 h. The volatiles are removed under reduced pressure and the residue is partitioned between EA and saturated NH4Cl solution. The organic phase is dried over MgSO4 and concentrated to give the desired intermediate as a colorless solid. LCMS (A): t R =0.89min;[M+H]+=478.17. 1 H NMR (500MHz, DMSO-d6) δ:12.17-13.30(m, 1H), 8.89(s, 1H), 7.84(dd, J 1 = 9.0Hz, J 2 =6.8Hz, 2H), 7.32-7.36(m, 4H), 5.54(s, 1H), 5.15(dd, J 1 = 10.7Hz, J 2 =3.5Hz, 1H), 4.45-4.52(m, 2H), 4.08-4.16(m, 2H), 4.02(d, J=9.4Hz, 1H), 3.93(m, 1H).

[0139] Intermediate 9a: (2S,4aR,6R,7R,8S,8aR)-7-acetoxy-2-phenyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Intermediate 8a (1.13 g, 2.37 mmol, 1 eq) is dissolved in DCM (30 mL) and TEA (1.3 mL, 9.47 mmol, 4 eq) and acetic anhydride (0.447 mL, 4.73 mmol, 2 eq) are added. The mixture is stirred o / n at rt. Saturated NH4Cl solution (20 mL) is added and the resulting mixture is stirred at rt for 10 min. The resulting precipitate is filtered and washed with DCM and water. The crude product, which still contains some salts, is dried under hv. Therefore, the solid is washed with citric acid solution (10%) and water and dried again under hv. LCMS (A): t R = 0.94min;[M+H]+ = 520.16.

[0140] Preparation of intermediates of structure 7 and structure 2 Intermediates of structure 7 are prepared by a) reductive amination of 2-aminocyclohexanol or 2-aminocycloheptanol with an aldehyde, b) alkylation with an alkylhalogenide, or c) by epoxide ring opening, as shown below.

[0141] [ka] Intermediate 10: (1S,2S)-2-((3-chlorobenzyl)amino)cyclohexan-1-ol To a solution of cis-2-aminocyclohexanol hydrochloride (100 mg, 0.868 mmol, 1 eq) in DCM / MeOH 4 / 1 (2.5 mL) is added 3-chlorobenzaldehyde (0.109 mL, 0.955 mmol, 1.1 eq) at rt. To the resulting solution is added sodium cyanoborohydride (68.9 mg, 1.04 mmol, 1.2 eq) at rt under nitrogen and the solution is stirred at rt for 4 h. Sodium cyanoborohydride (28.7 mg, 0.434 mmol, 0.5 eq) is added again at rt and the mixture is stirred at rt overnight. The mixture is quenched with water and basified with 25% aq. NH4OH solution. The mixture is extracted twice with DCM, the organic layers are combined and evaporated. The residue is redissolved in MeCN and basified with aq. 25% NH4OH solution. The product is purified by prep LCMS (I). The product-containing fractions are lyophilized to give the desired amino alcohol as a colorless solid. LCMS (A): R = 0.58min;[M+H]+ = 240.25.

[0142] The following intermediates are prepared analogously to the preparation of intermediate 10:

[0143] [Table 6] Preparation of silyl-protected compounds of structure 2: Compounds of structure 7 can be further protected at the hydroxy group according to the following methods: Intermediate 31: (1S,2S)-N-(2-(trifluoromethyl)benzyl)-2-((trimethylsilyl)oxy)cyclohexan-1-amine To a solution of intermediate 15 (556 mg, 2.03 mmol, 1 eq) and 2,6-lutidine (0.479 mL, 4.07 mmol, 2 eq) in dry DCM (10 mL) at 0 °C, trimethylsilyl trifluoromethanesulfonate 99% (0.558 mL, 3.05 mmol, 1.5 eq) is added dropwise. The mixture is stirred at 0 °C for 5 min and then warmed to rt. The mixture is quenched with water and extracted twice with DCM. The organic layers are combined, dried using a phase separator and then concentrated under reduced pressure. The crude is adsorbed onto isolute and purified by FC CombiFlash (12 g RediSep column, 0-100% EA in hept in 10 min) to give the title intermediate (545 mg) as a colorless oil. LCMS (B): t R = 1.41min;[M+H]+ = 346.23.

[0144] Intermediate 32: (1S,2S)-2-((tert-butyldimethylsilyl)oxy)-N-(2-(trifluoromethyl)benzyl)cyclohexan-1-amine To a solution of intermediate 15 (2000 mg, 7.32 mmol, 1 eq) and 2,6-lutidine (1.7 mL, 14.6 mmol, 2 eq) in dry DCM (80 mL) at 0 °C, tert-butyldimethylsilyl trifluoromethanesulfonate (2.52 mL, 11 mmol, 1.5 eq) is added dropwise. The mixture is stirred at 0 °C for 5 min and then warmed to rt. The mixture is quenched with water and extracted twice with DCM. The organic layers are combined, dried using a phase separator and then concentrated under reduced pressure. The crude is adsorbed onto isolute and purified by FC CombiFlash (40 g RediSep column, 0-100% EA in hept in 10 min) to give the title intermediate as a yellowish oil. LCMS (A): t R = 0.96min;[M+H]+ = 388.27.

[0145] The following intermediates are prepared similarly:

[0146] [Table 7]

[0147] [Table 8] Intermediate 53: (1S,2S)-2-(((4-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)cyclohexan-1-ol Step 1: (4-(trifluoromethyl)pyrimidin-5-yl)methanol 4-(Trifluoromethyl)pyrimidine-5-carboxylic acid (1000 mg, 5.21 mmol, 1 eq) is dissolved in THF (26 mL, 26 mmol, 5 eq) and cooled to -10 °C (dry ice bath). 4-Methylmorpholine (1.17 mL, 10.4 mmol, 2 eq) is added at -15 to -10 °C, then ethyl chloroformate (0.77 mL, 7.81 mmol, 1.5 eq) is added at an internal temperature of -20 to -10 °C. THF (10 mL) is added slowly, keeping the internal temperature below -10 °C to improve stirring. The mixture is kept at -10 °C for 30 min. After 30 min, sodium borohydride (761 mg, 19.5 mmol, 3 eq) is added at -10 °C and stirring is continued at this temperature for 5 min. The dry ice bath is then replaced with an ice bath and the mixture is stirred at 0 °C for 1 h. The reaction mixture is quenched with water (30 mL), acidified to pH 4-5 with 10% citric acid, then extracted with n-butanol (3x). The organic layers are combined, dried over MgSO4, filtered and evaporated to give a crude orange oil that still contains some salts. The mixture is suspended in DCM and the salts are filtered off. The filtrate is concentrated and the residue is purified by FC CombiFlash (12 g RediSep column, 10-100% EA in hept). The intermediate alcohol is isolated as a yellow oil. LCMS (A):t R = 0.49min;[M+H]+ = 220.3.

[0148] Step 2: 4-(trifluoromethyl)pyrimidine-5-carbaldehyde The above alcohol (365 mg, 2.05 mmol, 1 eq) was dissolved in DCM (15 mL). To the reaction mixture, add activated manganese(IV) oxide (3001 mg, 29.3 mmol, 14.32 eq) at rt. The mixture is stirred o / n at rt. The mixture is filtered through a glass fiber filter and the filtrate is evaporated to give the title aldehyde as a yellow oil.

[0149] Step 3: (1S,2S)-2-(((4-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)cyclohexan-1-ol (1S,2S)-2-Aminocyclohexanol (150 mg, 1.26 mmol, 1 eq) and the above aldehyde (245 mg, 1.39 mmol, 1.1 eq) are dissolved in DCM / MeOH 4 / 1 (5 mL) and sodium cyanoborohydride (100 mg, 1.52 mmol, 1.2 eq) is added portionwise at rt. The mixture is stirred at rt for 3 h. The mixture is diluted with DCM and carefully quenched with water. The mixture is basified with 25% NH4OH solution and the layers are separated (phase separator). The organic layer is concentrated and the crude is purified by FC (CombiFlash, 4 g RediSep column, 0-10% MeOH in EA) to give the title intermediate as a yellow oil. LCMS (A):t R = 0.46min;[M+H]+ = 276.27.

[0150] Intermediate 54: rac-N-((1R * ,2R * )-2-((tert-butyldimethylsilyl)oxy)cyclohexyl)-3,4-difluoroaniline Process 1: rac-(1R * ,2R * )-2-((3,4-difluorophenyl)amino)cyclohexan-1-ol Cyclohexene oxide (0.258 mL, 2.5 mmol, 1 eq) and 3,4-difluoroaniline (391 mg, 3 mmol, 1.2 eq) are mixed with water (4 mL) and heated o / n at 90° C. The mixture is diluted with water and EA, the organic phase is dried over MgSO4 and concentrated. The product is purified by FC (hept / EA 4:1-1:1) to give the desired amino alcohol as a brownish oil. LCMS (A): R = 0.71 min; [M+H] + = 228.24.

[0151] Step 2: rac-N-((1R * ,2R * )-2-((tert-butyldimethylsilyl)oxy)cyclohexyl)-3,4-difluoroaniline To a solution of the intermediate from step 1 (320 mg, 1.41 mmol, 1 eq) and 2,6-lutidine (0.328 mL, 2.82 mmol, 2 eq) in dry DCM (14.1 mL) is added tert-butyldimethylsilyl trifluoromethanesulfonate (0.485 mL, 2.11 mmol, 1.5 eq) dropwise at 0 °C for 5 min. The mixture is diluted with 10 mL water. The layers are separated (phase separator) and the aqueous phase is re-extracted twice with 5 mL DCM. The organic layer is evaporated and dried o / n under hv. The crude is purified by FC (CombiFlash, 12 g Redi-Sep column, 0-50% EA in hept) to give the desired intermediate as an orange oil. LCMS (A): t R = 1.27min;[M+H]+ = 342.00.

[0152] The following compound is prepared analogously to intermediate 54, steps 1 and 2.

[0153] [Table 9]

[0154] [Table 10]

[0155] [Table 11] Intermediate 98: Methyl (4aR,6R,7R,8R,8aR)-7-hydroxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylate To a solution of intermediate 5a (120 mg, 0.279 mmol, 1 eq) in DMF (2.4 mL) is added NaH (60% dispersion in mineral oil, 11.3 mg, 0.282 mmol) at 0 °C. The reaction mixture is stirred at rt for 0.5 h. Dimethyl sulfate (0.029 mL, 0.307 mmol) is added and the reaction mixture is stirred at rt for 1 h. The mixture is cooled, quenched with water and extracted twice with ethyl acetate. The organic layers are combined, washed with saturated aqueous NaCl (10 mL), dried over MgSO4 and evaporated. The product is purified by CombiFlash, 24 g RediSep column, 0-100% ethyl acetate in hexane. The product is isolated as a colorless solid. LCMS (A): t R =0.88min;[M+H]+=444.20.

[0156] Intermediate 99: Methyl (4aR,6R,7R,8R,8aR)-7-(2-(tert-butoxy)-2-oxoethoxy)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylate To a solution of intermediate 98 (650 mg, 1.47 mmol, 1 eq) in DMF (15 mL) at rt is added tert-butyl bromoacetate (409 mg, 2.05 mml) and NaH (60% dispersion in mineral oil, 78 mg, 2.05 mmol). The reaction mixture is stirred at rt for 2.5 h. The mixture is cooled, quenched with water and extracted twice with ethyl acetate. The organic layers are combined, washed with saturated aqueous NaCl (10 mL), dried over MgSO4 and evaporated. The product is purified by CombiFlash, 24 g RediSep column, 0-100% ethyl acetate in hexane. The product is isolated as a colorless solid. LCMS (A):t R = 1.05min;[M+H]+ = 558.01.

[0157] Intermediate 100a: (4aR,6R,7R,8R,8aR)-7-(2-(tert-butoxy)-2-oxoethoxy)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid Intermediate 99 (673 mg, 1.21 mmol, 1 eq) in THF, MeOH, HO (2 To a solution in 1 mL of 3:2:1 at 0° C. is added LiOH (44 mg, 1.81 mmol) and the mixture is stirred for 1 h. An additional amount of LiOH (44 mg, 1.81 mmol) is added and the mixture is stirred for 0.5 h. The pH is maintained at 4 by adding 1 N aq. HCl and the mixture is extracted twice with ethyl acetate. The combined organic layers are washed with saturated aqueous NaCl (10 mL), dried over MgSO4 and evaporated. The product is isolated as a colorless solid. LCMS (A):t R =0.96min;[M+H]+=543.99.

[0158] Intermediate 100b: (4aR,6R,7R,8R,8aR)-7-(2-(tert-butoxy)-2-oxoethoxy)-8-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid This compound is prepared from the corresponding acid analogously to intermediate 100a.

[0159] Intermediate 101: Tert-butyl 2-(((4aR,6R,7R,8R,8aR)-6-(((1S,2S)-2-((tert-butyldimethylsilyl)oxy)cyclohexyl)(3,5-dichlorophenyl)carbamoyl)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)acetate The compound is prepared from intermediate 100a and intermediate 56 according to general procedure B. LCMS (A): R = 1.43min;[M+H]+ = 899.17.

[0160] Intermediate 102: Tert-butyl 2-(((2R,3R,4S,5R,6R)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclohexyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl)oxy)acetate To a solution of intermediate 101 (450 mg, 0.50 mmol) in 1,4-dioxane (24 mL) and water (12 mL) at 0° C., TFA (3.1 mL) is added dropwise. The reaction mixture is stirred at rt for 16 h. The pH is maintained at 8 by adding Sat. aq. NaHCO3 and the mixture is extracted twice with ethyl acetate. The combined organic layers are washed with saturated aqueous NaCl (10 mL), dried over MgSO4 and evaporated. The product is isolated as a yellowish oil. LCMS (A):t R = 1.10min;[M+H]+ = 745.19.

[0161] The following intermediates are prepared in two steps from the corresponding starting materials analogously to acid 6a.

[0162] [Table 12]

[0163] [Table 13]

[0164] [Table 14]

[0165] [Table 15] B. Preparation of Examples General procedure A: Amide coupling using T3P To a solution of the acid component (1 eq) and the amine intermediate (1.1 eq) in DMF (5 mL / mmol) DIPEA (1.5 eq) and T3P (50% solution in EA, 1.5 eq) are added and the mixture is stirred at rt until complete conversion. After aqueous workup (EA / dil HCl) the product is purified as described in the general method.

[0166] General procedure B: Amide coupling using POCl3 / pyridine To a solution of the acid component (1 eq) and the amine intermediate (1.2 eq) in DCM (10 mL / mmol) at 0° C., phosphorus(V) oxychloride (1 M solution in pyridine, 0.451 mL, 0.451 mmol, 1 eq) is added dropwise within 2-3 min. The mixture is stirred at 0° C. for 10 min and then slowly warmed to rt. After completion of the reaction, the mixture is quenched with 10% citric acid and extracted twice with EA. The organic layer is washed with brine. The combined organic layers are dried over magnesium sulfate, filtered and concentrated. The product is purified as described in General Methods.

[0167] General procedure C: Deprotection with aq AcOH The protected intermediates (acetal and / or silyl Pg) (1 eq) are refluxed in AcOH / H2O 1:1 (5 mL / mmol) until the reaction is complete. The products are purified as described in the general method.

[0168] General procedure D: Deprotection with CSA in MeOH CSA (0.1 eq) is added to the isopropylidene protected intermediate (1 eq) in MeOH (5 mL / mmol) and heated under reflux until the reaction is complete. The product is purified as described in the general method.

[0169] General procedure E: Acetate deprotection with K2CO3 in MeOH K2CO3 (0.1 eq) is added to the acetate protected intermediate (1 eq) in MeOH (5 mL / mmol) and stirred at rt until the reaction is complete. The product is purified as described in the general method.

[0170] The compounds of the Examples (Ex.) in Table 1 below were prepared by coupling with acids 1-9, 98-128 and amines 10-97, 129-133 using either Process A or Process B described above. The final compound is prepared by applying method C, D or E. Deprotection using method C, D or E gives the final compound.

[0171] [Table 16]

[0172] [Table 17]

[0173] [Table 18]

[0174] [Table 19]

[0175]

Table 20

[0176]

Table 21

[0177]

Table 22

[0178]

Table 23

[0179]

Table 24

[0180]

Table 25

[0181]

Table 26

[0182]

Table 27

[0183]

Table 28

[0184]

Table 29

[0185] [Table 30]

[0186] [Table 31]

[0187] [Table 32]

[0188] [Table 33]

[0189] [Table 34]

[0190] [Table 35] Example 195: 2-(((2R,3R,4S,5R,6R)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclohexyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl)oxy)acetic acid To a solution of intermediate 102 (373 mg, 0.5 mmol, 1 eq) in DCM (3 mL) at rt is added 2M TFA (1.20 mL) and the reaction mixture is stirred at rt for 3 h. The solvent is evaporated. The product is isolated as a TFA salt. LCMS (A):t R =0.90min;[M+H]+=689.18.

[0191] Example 196: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide To a solution of Example 195 (54 mg, 0.067 mmol, 1 eq) in THF (3 mL) at 0° C. is added a 2M solution of BH3.Me2S in THF (0.14 mL, 4.2 eq) and the reaction mixture is stirred at rt for 24 h. MeOH (1 mL) and saturated aqueous NH4Cl (15 mL) are added and the mixture is extracted twice with ethyl acetate. The organic layers are combined and washed with saturated N Wash with aqueous aCl (10 mL) and evaporate. Purify the product by LC-MS (I). Isolated the product as a colorless solid. LCMS (A): t R =0.90min;[M+H]+=689.17.

[0192] Example 124: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-morpholino-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide To a solution of Example 195 (50 mg, 0.049 mmol, 1 eq) in DMF (1 mL) at rt, HATU (0.040 mL, 2 eq), morpholine (9 μl, 2 eq) and DIPEA (42 μl, 5 eq) are added and the reaction mixture is stirred at rt for 0.5 h. The reaction mixture is purified by LC-MS (I). The product is isolated as a colorless solid. LCMS (A): t R = 0.95min;[M+H]+ = 757.99.

[0193] The following compounds are prepared from Example 195 and the corresponding amines in analogy to Example 124:

[0194] Example 125: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-((S)-3-hydroxypyrrolidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide LCMS(A):t R =0.86min;[M+H]+=758.19.

[0195] Example 126: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-((R)-3-hydroxypyrrolidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide LCMS(A):t R =0.86min;[M+H]+=758.18.

[0196] Example 127: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-(4-hydroxypiperidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide Step 1: (2R,3R,4S,5R,6R)-3-(2-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-oxoethoxy)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide is prepared from Example 195 and 4-((tert-butyldimethylsilyl)oxy)piperidine according to the procedure described for Example 124. LCMS (A):t R = 1.23min;[M+H]+ = 886.36.

[0197] Step 2: To a solution of the above silyl ether (28 mg, 0.032 mmol) in dioxane (3 mL) and water (1.45 mL), TFA (0.4 mL) is added and the reaction mixture is stirred at rt for 1.5 h. Ethyl acetate (10 mL) and saturated aqueous NaHCO3 (15 mL) are added to maintain pH 8, the aqueous phase is separated and extracted twice with ethyl acetate. The organic layer is Combine and evaporate. Purify the product by LC-MS (I). Isolated the product as a colorless solid. LCMS (A): t R =0.88min;[M+H]+=772.17.

[0198] Example 128: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-3-(2-(3-hydroxyazetidin-1-yl)-2-oxoethoxy)-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide This compound is prepared in a two-step process similar to Example 127. LCMS(A):t R =0.85min;[M+H]+=744.09.

[0199] Example 203: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-morpholinophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide Step 1: To a solution of intermediate 6a (0.100 mg, 0.226 mmol, 1 eq), K2CO3 (0.156 mg, 1.13 mmol) in DMSO (4 ml) at rt, morpholine (0.100 mL, 1.13 mmol) is added and the reaction mixture is stirred at 130 °C for 40 h. Morpholine (0.100 mL) is added and the mixture is stirred for 5 days. Ethyl acetate and saturated aqueous NaH4Cl are added to maintain pH 6-7, the aqueous phase is separated and extracted twice with ethyl acetate. The organic layers are combined and evaporated. The product is purified by LC-MS (I). The product is isolated as a colorless solid. LCMS (A): t R =0.86min;[M+H]+=511.03.

[0200] Step 2: Amide coupling of the acid from step 1 with amine 56 is carried out according to procedure B. LCMS (A):t R =1.42min;[M+H]+=866.09.

[0201] Step 3: The product of step 2 is deprotected according to the method described for Example 127, step 2. LCMS (A): t R = 1.00min;[M+H]+ = 712.03.

[0202] Example 204: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-((3-hydroxypropyl)amino)phenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide Example 204 is prepared analogously to Example 203, using azetidine instead of morpholine in step 1. LCMS (A): t R = 0.93 min; [M + H] + = 700.01.

[0203] II. Biological Testing Inhibitory activity of the compound (IC 50 ) Evaluation The inhibitory activity of the compounds is determined in a competitive binding test. This spectrophotometric assay measures the binding of biotin-labeled human Gal-3 (hGal-3) or human Gal-1 (hGal-1), respectively, to the glycoprotein asialofetuin (ASF) adsorbed on microplates (Proc Natl Acad Seis USA. 2013 Mar 26;110(13):5052-7). Alternatively and preferably, a version of human Gal-1 in which all six cysteines are replaced by serine may be used.

[0204] 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.

[0205] 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.

[0206] Calculated IC 50Values ​​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.

[0207] [Table 36]

[0208] [Table 37]

[0209] [Table 38]

[0210] [Table 39]

Claims

1. A compound of formula (I) or a pharma- ceutically acceptable salt thereof: 【Chemistry 1】 (In the formula, n represents an integer of 1 or 2; Ar １ teeth, aryl, substituted by 1, 2, 3, 4 or 5 substituents, said substituents being selected from the group consisting of halogen; methyl; cyano; methoxy; trifluoromethyl; trifluoromethoxy; NR Ｎ１１ R Ｎ１２ (R Ｎ１１ represents hydrogen, and R Ｎ１２ is hydroxy-C ２－３ -alkyl or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl selected from morpholin-4-yl, azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl, Cyclyl is unsubstituted or substituted with one hydroxyl; - a 5- or 6-membered heteroaryl, which is independently unsubstituted or substituted with 1 or 2 substituents, said substituents being independently selected from halogen, methyl, cyano and methoxy; or - 9- or 10-membered heteroaryl, which 9- or 10-membered heteroaryl is independently unsubstituted or substituted by one methyl; represents; R １ teeth, - hydroxy; - C １－３ -alkoxy; - -O-CO-C １－３ - alkyl; - -O-CH ２ -CH ２ -OH; Or, - -O-CH ２ -CO-R １Ｘ (R １Ｘ は、 -- -hydroxy; --morpholin-4-yl; Or, -- -NR Ｎ２１ R Ｎ２２ (R Ｎ２１ and R Ｎ２２ together with the nitrogen atom to which they are attached form a 4-6 membered heterocyclyl selected from azetidin-1-yl, pyrrolidin-1-yl and piperidin-1-yl, said 4-6 membered heterocyclyl being substituted by one hydroxy; ) ; represents; L represents a direct bond, methylene or ethylene; Ar ２ teeth, - phenyl or 5- or 6-membered heteroaryl, which is independently unsubstituted or substituted by 1, 2 or 3 substituents, said substituents being selected from the group consisting of C １－６ -Alkyl, C ３－６ -cycloalkyl, -CH ２ -C ３－６ -Cycloalkyl, C １－３ -fluoroalkyl, C １－３ -fluoroalkoxy, C １－３ - phenyl or 5- or 6-membered heteroaryl independently selected from alkoxy, halogen, morpholin-4-yl, amino, ethynyl and cyano; a 9-membered bicyclic heteroaryl or a 10-membered bicyclic heteroaryl, which 9- or 10-membered bicyclic heteroaryl is independently unsubstituted or substituted with 1 or 2 substituents independently selected from methyl, methoxy and halogen; or - naphthyl; represents.)

2. 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; 2. The compound of claim 1 or a pharma- ceutically acceptable salt thereof.

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

2. The compound of claim 1, wherein R represents a phenyl group;

4. R １ A compound according to any one of claims 1 to 3, or a pharma- ceutically acceptable salt thereof, wherein: represents methoxy.

5. 5. The compound according to any one of claims 1 to 4, or a pharma- ceutically acceptable salt thereof, wherein L represents a direct bond.

6. Ar ２ but, phenyl, unsubstituted or substituted by 1 or 2 substituents, said substituents being C １－４ -Alkyl, C １－３ -fluoroalkyl, C １－３ - phenyl, independently selected from alkoxy, halogen, ethynyl and cyano; or - a 5- or 6-membered heteroaryl, which is independently unsubstituted or substituted by 1 or 2 substituents, said substituents being selected from the group consisting of C １－４ -Alkyl, -CH ２ -C ３－６ -Cycloalkyl, C １－３ -fluoroalkyl, C １－３ - 5- or 6-membered heteroaryl independently selected from alkoxy, halogen, morpholin-4-yl and amino; The compound according to any one of claims 1 to 5, or a pharma- ceutically acceptable salt thereof.

7. Ar ２ but: phenyl, substituted by 1 or 2 substituents, said substituents being C １－３ - phenyl, independently selected from fluoroalkyl and halogen; or - 5- or 6-membered heteroaryl, which is independently substituted by 1 or 2 substituents, said substituents being selected from the group consisting of: １－４ -Alkyl and C １－３ - a 5- or 6-membered heteroaryl independently selected from fluoroalkyl; The compound according to any one of claims 1 to 5, or a pharma- ceutically acceptable salt thereof.

8. Fragment-L-Ar ２ but: 【Chemistry 3】 【Chemistry 4】 【Chemistry 5】 【Chemistry 6】 The compound according to any one of claims 1 to 4, or a pharma- ceutically acceptable salt thereof.

9. 9. The compound according to any one of claims 1 to 8, wherein n represents an integer of 1; or a pharma- ceutically acceptable salt thereof.

10. The compound is (2R,3R,4S,5R,6R)-N-benzyl-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorobenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-ethynylbenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-phenethyl-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(4-chlorobenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2-chlorobenzyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3-chloropyridin-4-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((2-(trifluoromethyl)pyridin-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((4-(trifluoromethyl)pyridin-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-(trifluoromethyl)benzyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2-chlorobenzyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((3-(trifluoromethyl)pyridin-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((2-methyl-1H-imidazol-4-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((2-amino-4-chlorothiazol-5-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl) (1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(isoxazol-4-ylmethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((5-chlorofuran-2-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(isothiazol-4-ylmethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-imidazol-4-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((2-bromothiazol-4-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((2-morpholinothiazol-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((5-chlorothiophen-2-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((5-chlorothiazol-2-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-pyrazol-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((3-(trifluoromethyl)pyridin-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxy (2-(trifluoromethyl)pyridin-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((4-(trifluoromethyl)pyrimidin-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((4,6-dimethoxypyrimidin-5-yl)methyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((4-methylpyrimidin-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((5-methyl-1H-imidazol-4-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((4-chloroisothiazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-pyrazol-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((3-methylthiophen-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-pyrrol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3-chlorothiophen-2-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxy (4-methylthiazol-5-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-imidazol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((2-methylthiophen-3-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-methoxybenzyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2,6-dimethoxybenzyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-imidazol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-methyl-1H-imidazol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-((1-ethyl-1H-pyrazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-((1-isopropyl-1H-pyrazol-5-yl)methyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((1-(cyclopropylmethyl)-1H-pyrazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4, 5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-((1-methyl-1H-indol-2-yl)methyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)((1-methyl-1H-pyrazol-5-yl)methyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3-chlorobenzyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-((6-fluoro-3-methoxyquinoxalin-5-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3-chloroquinolin-2-yl)methyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-2-(((1S,2S)-2-hydroxycyclohexyl)(2-(trifluoromethyl)benzyl)carbamoyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-N-(2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-methoxyphenyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluoro-2-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(5-fluoro-2-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-methoxyphenyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyanophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(methoxy-d3)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(5-chloro-2-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-4-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-4-(trifluoromethyl)phenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-4-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide D; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-methylbenzo[d]thiazol-6-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-(trifluoromethyl)phenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,4-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-4-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-phenyl-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-methoxyphenyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[b]thiophen-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide D; (2R,3R,4S,5R,6R)-N-(5-chloro-2-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2,5-dimethylbenzo[d]thiazol-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(2-chlorobenzo[d]thiazol-6-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(5-bromo-2-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(4-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(3-(trimethylsilyl) fluoromethyl)phenyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-fluoro-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-fluoro-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(m-tolyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(2-methyl-1H-benzo[d]imidazol-6-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-6-yl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carbo oxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-fluorophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyanophenyl)-5-hydroxyphenyl Droxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-5-yl)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole -1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-fluorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxyphenyl) (methoxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(benzo[d]thiazol-6-yl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; 2-(((2R,3R,4S,5R,6R)-2-((3-chloro-5-cyanophenyl)((1S,2S)-2-hydroxycyclohexyl)carbamoyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)oxy)acetic acid; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-morpholino-2-oxoethoxy)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4,5-difluoro-2-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3-methoxyphenyl) -1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluoro-5-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(2-methylbenzo[d]thiazol-6-yl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(4-fluoronaphthalen-1-yl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl)-N-(2,3-difluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(pyridin-2-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(naphthalen-2-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3- Triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-N-(naphthalen-1-yl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(1,5-dimethyl-1H-pyrazol-3-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycycloheptyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycycloheptyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-morpholino-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-((S)-3-hydroxypyrrolidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazolidine (1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-((R)-3-hydroxypyrrolidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-(2-(4-hydroxypiperidin-1-yl)-2-oxoethoxy)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-3-(2-(3-hydroxyazetidin-1-yl)-2-oxoethoxy)-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; 2-(((2R,3R,4S,5R,6R)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclohexyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl)oxy)acetic acid; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-morpholinophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; Or, (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-((3-hydroxypropyl)amino)phenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclohexyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; 2. The compound of claim 1, wherein:

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

12. A compound according to any one of claims 1 to 10, or a pharma- ceutically acceptable salt thereof, for use as a medicament.

13. 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; digestive diseases and disorders; urinary tract 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 10 or a pharma-ceutically acceptable salt thereof.

14. 13. Use of a compound according to any one of claims 1 to 10, 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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