Novel galactoside inhibitors of galectins

Abstract

TIFF2022538635000465.tif4473 The present invention relates to D-galactopyranose compounds of formula (1), wherein the pyranose ring is α-D-galactopyranose, which are high-affinity galectin-1 and / or galectin-3 inhibitors for use in the treatment of inflammation; fibrosis; scarring; keloid formation; abnormal scar formation; surgical adhesions; septic shock; cancer; metastatic cancer; autoimmune diseases, metabolic disorders; heart disease; heart failure; pathological angiogenesis; eye diseases; atherosclerosis; metabolic diseases; type I diabetes; type II diabetes; insulin resistance; diastolic heart failure; asthma; and liver damage.

Description

[Technical Field]

[0001] The present invention relates to novel compounds, their use as pharmaceuticals and for the manufacture of medicaments for the treatment of cancer, fibrosis, scarring, keloid formation, abnormal scarring, surgical adhesions, pathological angiogenesis, ocular diseases, HIV-1 disease, inflammation or transplant rejection in mammals. The present invention also relates to pharmaceutical compositions comprising the novel compounds. [Background technology]

[0002] Galectins are proteins with a distinctive carbohydrate recognition domain (CRD) (Leffler et al., 2004). This is a tightly folded β-sandwich of approximately 130 amino acids (approximately 15 kDa) with two distinct features: 1) a β-galactose-binding site and 2) sufficient similarity of a sequence motif of approximately seven amino acids, the majority of which (approximately six residues) constitutes the β-galactose-binding site. However, sites adjacent to the β-galactose site are required for tight binding of natural saccharides, and these different preferences confer different fine specificities to galectins for natural saccharides.

[0003] The recent completion of the human, mouse, and rat genome sequences has revealed that there are approximately 15 galectins and galectin-like proteins in a single mammalian genome, with little variation between species (Leffler et al., 2004).

[0004] Galectin subunits can contain one or two CRDs within a single peptide chain. The first category, mono-CRD galectins, can exist as monomers or dimers (two types) in vertebrates. By far the best-studied galectins are the dimeric galectin-1 and galectin-3, which are monomers in solution but can aggregate into multimers upon encountering ligands (Lepur et al., 2012). These were the first galectins discovered and are abundant in many tissues.

[0005] Currently, there are over 5700 publications on galectins in PubMed, the majority of which, as mentioned above, are related to galectin-1 (over 1400) and galectin-3 (over 2800). Strong evidence suggests roles for galectins, for example, in inflammation and cancer, as well as in development (Blidner et al., 2015; Ebrahim et al., 2014).

[0006] Galectins are synthesized as cytosolic proteins without a signal peptide on free ribosomes. Their N-termini are acetylated (a typical modification of cytosolic proteins), allowing them to reside in the cytosol for extended periods (atypical for secreted proteins). From there, galectins can be targeted to the nucleus, specific cytosolic sites, or secreted (inducibly or constitutively) by a non-canonical (non-ER-Golgi) pathway (first shown for galectin-1 (Cooper and Barondes, 1991)), possibly by mechanisms that are not yet known, similar to the transport of IL-1 (Leffler et al., 2004; Arthur et al., 2015). Galectins can also function in all these compartments; for galectin-1, compelling evidence published in well-respected journals supports roles in RNA splicing in the nucleus, H-RAS activation in the cytosol, accumulation around disrupted vesicles, and various extracellular effects on cell signaling and adhesion (Elola et al., 2015; Aits et al., 2015; Blanchard et al., 2016). Other galectins can also act in the cytosol by enhancing apoptosis and regulating cell cycle and differentiation in certain cells. Most galectins also act extracellularly by cross-linking glycoproteins (e.g., laminin, integrins, and IgE receptors), likely forming supramolecularly ordered arrays (Elola et al., 2015), which can regulate cell adhesion and induce intracellular signals. In this context, recent evidence has shown that the molecular mechanisms underlying these galectin functions involve the formation of intramembrane microdomains (lattices), which in turn affect the intracellular trafficking and cell surface presentation of glycoprotein receptors (Elola et al., 2015). This has been demonstrated in cell cultures, null mutant mice, and animals treated with galectins or galectin inhibitors.

[0007] Galectin-1, the first discovered and second most widely studied galectin, is expressed in all tissues with certain preferences, but not exclusively in cells of mesenchymal origin, such as fibroblasts and lymphocytes. It is involved in regulating cell proliferation, adhesion, signal transduction, differentiation, development, the immune system, and host-pathogen interactions (Blanchard et al., 2016). The expression profile of galectin-1 during various stages of cancer progression and its role in the tumor microenvironment have been thoroughly reviewed.

[0008] Galectin-1 is involved in a variety of phenomena, and inhibitors may therefore have multiple uses. It is easy to perceive this as a lack of specificity or lack of scientific focus. Therefore, an analogy with aspirin and cyclooxygenase (COX-I and COX-II) is useful. COX produces precursors to a wide variety of prostaglandins and is therefore involved in a variety of biological mechanisms. Their inhibitors, aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs), also have broad and diverse effects. Despite this, these inhibitors are highly useful medically, with several distinct specific utilities.

[0009] Thus, if galectins, like COXs, are part of some (as yet unknown) fundamental biological regulatory mechanism, it is likely that they are "used naturally" in different situations and for different purposes. Galectin inhibitors, like NSAIDs, are expected to tip the balance slightly rather than decimate the entire system.

[0010] Galectin-1 in immunity and inflammation Galectin-1 has been found to primarily have immunosuppressive and anti-inflammatory roles (Elola et al., 2015), but may also be pro-inflammatory in some cases. Galectin-1 binds to specific glycosylation patterns on T helper cells and selectively induces apoptosis in activated Th1 and Th17 cells (Perillo et al., 1995) (Toscano, MA et al., 2007). The immunosuppressive effects of galectin-1 suggest that it itself may be a potential treatment for autoimmune and other inflammatory conditions. Conversely, inhibiting its immunosuppressive effects, for example in cancer, has also been proposed as a treatment, as described below.

[0011] Galectin-1 in angiogenesis. Like galectin-3, galectin-1 has been shown to promote angiogenesis under certain circumstances through its carbohydrate-binding activity (Hockl et al., 2016). Of particular interest is the observation that it can promote tumor angiogenesis through a pathway similar to that of VEGF. Therefore, inhibition of galectin-1 could be antiangiogenic when anti-VEGF-based inhibition fails. The discovery that the antiangiogenic peptide Anginex (and related compounds) binds to galectin-1 suggests another mechanism for galectin-1 in angiogenesis, although the details remain unclear; Anginex has been described in some reports as inhibiting galectin-1 activity, while others have described it as enhancing its carbohydrate-binding activity.

[0012] Galectin-1 in fibrosis-related conditions The idea of ​​a possible role for galectin-3 in fibrosis comes from cell and ex vivo studies of macrophage differentiation (Mackinnon et al., 2008) and in vivo studies of macrophage differentiation and myofibroblast activation (Mackinnon et al., 2012). Briefly, the hypothesis is as follows: galectin-3 prolongs cell surface residence and thus enhances the responsiveness of TGF-β receptors (Partridge et al., 2004), which in turn has been shown to regulate alternative macrophage differentiation into M2 macrophages and myofibroblast activation. Galectin-1 has also been suggested to play a role in fibrosis, including through TGF-β-related mechanisms, although the evidence is less clear than for galectin-3.

[0013] Therefore, since galectin-1 is also a good candidate to be an endogenous enhancer of TGF-β signaling and myofibroblast activation (Kathiriya et al.), galectin-1 inhibitors may also be useful in the treatment of fibrosis and adverse tissue remodeling.

[0014] Galectin-1 in cancer. Numerous immunohistochemical studies have demonstrated altered expression of certain galectins in cancer (van den Brule et al. and Bidon et al., 2004b). For example, galectin-3 is now an established histochemical marker for thyroid cancer. Direct evidence for the role of galectin-3 in cancer comes primarily from a mouse model developed by Raz et al., but also from other models (Leffler et al., 2004b). In paired tumor cell lines (with decreased or increased galectin-3 expression), induction of galectin-3 resulted in more tumors and metastases, while inhibition of galectin-3 resulted in fewer tumors and metastases. Galectin-3 has been shown to enhance tumor growth by being anti-apoptotic, promote angiogenesis, or promote metastasis by affecting cell adhesion. Furthermore, recent evidence indicates that galectin-3 plays an important role in the tumor microenvironment (reviewed in (Ruvolo, 2015)). Galectin-3 is also thought to regulate interactions between tumor cells and immune cells such as T lymphocytes (T cells), and inhibition of galectin-3 has been shown to restore T cell activity (Demotte et al., 2010; Kouo et al., 2015; Melero et al., 2015). From the above, it is clear that inhibitors of galectin-3 may have beneficial anticancer effects. Indeed, saccharides that have been claimed but not proven to inhibit galectin-3 have been reported to have anticancer effects. In our own research, a CRD-containing galectin-3 fragment inhibited breast cancer in a mouse model by acting as a dominant-negative inhibitor (John et al., 2003). More recently, it has been demonstrated that inhibition of galectin-3 with small molecules indeed greatly enhances tumor cell sensitivity to radiation and standard proapoptotic drugs in cellular assays and ex vivo (Lin et al., 2009) and in vivo (Glinsky et al., 2009).

[0015] Galectin-1 is also frequently overexpressed in poorly differentiated cancer cells, and galectin-9 or its related galectins 4 and 8 can be induced in certain cancer types (Huflejt and Leffler, 2004; Leffler (eds.) 2004b). Galectin-1 induces apoptosis in activated T cells and has a significant immunosuppressive effect on autoimmune diseases in vivo (Rabinovich et al.; and Pace et al., Leffler (eds.) 2004b). Thus, overexpression of these galectins in cancer may help tumors defend themselves against T cell responses triggered by the host.

[0016] Galectin-1 and galectin-3 null mutant mice were established many years ago (Poirier, 2002). These mice are healthy and apparently reproduce normally under animal husbandry conditions. However, recent studies have revealed subtle phenotypes in neutrophil and macrophage function (see above) and bone formation in galectin-3 null mutants, and in nerve and muscle cell regeneration / differentiation in galectin-1 null mutants (Leffler et al., 2004; Poirier, 2002; Watt Leffler (ed.) 2004b). Galectin-7 and galectin-9 null mutant mice have recently been generated, and although these mice are also remarkably healthy under animal husbandry conditions, they have not yet been analyzed in detail. Differences in expression site, specificity, and other properties make it unlikely that different galectins can functionally replace each other. Findings in null mutant mice may indicate that galectins are not essential for basic vital functions, as can be observed under normal animal husbandry conditions. Alternatively, galectins may be optimizers of normal function and / or may be essential under stressful conditions not observed in animal husbandry. The lack of a strong effect in null mutant mice may make galectin inhibitors more advantageous as drugs. If galectin activity contributes to pathological conditions but not significantly to normal conditions, as suggested above, then galectin inhibition would have fewer undesirable side effects.

[0017] Therefore, drugs that target galectin-1 activity in cancer, such as immunosuppression or enhanced angiogenesis, may be useful anticancer treatments.

[0018] Known inhibitors Natural ligands Solid-phase binding and inhibition assays have identified several sugars and glycoconjugates capable of binding to galectins (reviewed by Leffler, 2001; Leffler et al., 2004). All galectins have a K of approximately 0.1–1 mM. d It binds to lactose at 100-150 mM. D-Galactose has a 50- to 100-fold lower affinity. N-acetyllactosamine and related disaccharides bind as well as lactose, but can bind worse or up to 10-fold better to certain galectins. Both galactose (10 mM) (Tejler et al. 2009) and lactose (190 μM) (van Hattum, 2013) have low affinity for galectin-1.

[0019] The natural sugars identified as galectin-1 ligands are susceptible to acidic and enzymatic hydrolysis in the stomach, making them unsuitable for use as active ingredients in pharmaceutical compositions. Furthermore, natural sugars are hydrophilic in nature and are not readily absorbed from the gastrointestinal tract after oral administration.

[0020] Galectin specificity Galectin specificity studies using inhibition by small natural sugars, as described above, showed that while all galectins bind lactose, LacNAc, and related disaccharides, galectin-3 binds much better to certain longer sugars (Leffler and Barondes, 1986). These longer sugars are characterized by the addition of an additional sugar residue at the C-3 position of the galactose (e.g., in lactose or LacNAc) bound in an elongated binding groove. The shape of this groove differs among galectins, suggesting that the same extension is not bound equally by different galectins.

[0021] Synthetic inhibitors A patent review covering galectin-1 inhibitors and their potential as therapeutic agents was recently published (Blanchard 2016). The small monosaccharides covered in this review are reported to have galectin-1 affinities similar to lactose at best. On the other hand, disaccharides, particularly thiodigalactoside (TDG), are reported to have high affinity for galectin-1 (T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285).

[0022] Sugars linked to amino acids with anticancer activity were first identified as natural compounds in serum, but synthetic analogs were subsequently prepared (Glinsky et al., 1996). Among these, lactose or galactose linked to amino acids inhibit galectins but with approximately the same potency as the corresponding underivatized sugars. Chlorin-conjugated lactose has been reported to have high affinity (0.54 μM) as measured by ELISA assay (Pandey et al., 2002; EP 1256586). A chemically modified form of citrus pectin, which inhibits galectin-3 (Platt and Raz, 1992), exhibits antitumor activity in vivo (Pienta et al., 1995; Nangia-Makker et al., 2002). Cluster molecules with up to four lactose moieties exhibited a strong multivalent effect when binding to galectin-3, but not to galectin-1 or galectin-5 (Vrasidas et al., 2003). Cyclodextrin-based glycoclusters containing seven galactose, lactose, or N-acetyllactosamine residues also exhibited a strong multivalent effect on galectin-3, but less so on galectins-1 and -7 (Andre et al., 2004). Starburst dendrimers (Andre et al., 1999) and glycopolymers (Pohl et al., 1999; David et al., 2004) multivalent with lactose residues have been described as galectin-3 inhibitors with slightly improved potency compared to lactose. Multivalent lactose derivatives have been shown to have a pronounced cluster effect on galectin-1 (Tejler et al., 2006). Furthermore, these compounds were selective over other galectins. Peptide-based compounds, such as Anginex and non-peptide topomimetics (Dings et al. 2012), have been reported to be allosteric galectin-1 inhibitors. The synthetic compounds identified as galectin-1 ligands are hydrophilic in nature and are not readily absorbed from the gastrointestinal tract after oral administration, making them unsuitable for use as active ingredients in pharmaceutical compositions.Furthermore, the compounds have moderate affinity and selectivity.

[0023] The natural oligosaccharides, glycoclusters, glycodendrimers, peptides, non-peptidic topomimetics, and glycopolymers mentioned above are too polar, too large to be absorbed, and in some cases large enough to induce an immune response in patients. Furthermore, they are susceptible to acidic and enzymatic hydrolysis in the stomach. Therefore, synthetic small molecules are needed.

[0024] Thiodigalactosides are synthetic, hydrolytically stable, yet polar inhibitors known to be nearly as efficient as N-acetyllactosamine (Leffler and Barondes, 1986). N-acetyllactosamine derivatives bearing aromatic amides or substituted benzyl ethers at C-3' have been demonstrated to be highly efficient inhibitors of galectin-3, with an unprecedented low IC of 4.8 μM. 50 These derivatives have a high affinity for galectins, a 20-fold improvement over natural N-acetyllactosamine disaccharides (Sorme et al., 2002; Sorme et al., 2003b, 2005). Due to the presence of the aromatic amide moiety, these derivatives are less polar overall and therefore more suitable as drugs for inhibiting galectins in vivo. Furthermore, C3-triazolylgalactosides have been demonstrated to be as potent inhibitors of several galectins as the corresponding C3-amides. Therefore, any appropriately structured galactose C3 substituent can confer enhanced galectin affinity.

[0025] However, C3-amido- and C3-triazolyl-derivatized compounds remain susceptible to hydrolysis in vivo due to the presence of glycosidic linkages in the galactose and N-acetyllactosamine sugar moieties, and although they are potent small molecule inhibitors of galectin-3, further improved affinity and stability are desirable. Therefore, inhibitors based on 3,3'-diamido- or 3,3'-ditriazolyl-derivatized thiodigalactosides, which lack the O-glycosidic hydrolytic and enzymatically labile bond, have been developed (Cumpstey et al., 2005b; Cumpstey et al., 2008; Salameh et al., 2010; WO 2005 / 113569 and U.S. Patent Application Publication No. 2007185041; WO 2005 / 113568; U.S. Patent No. 7,638,623; T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285). These inhibitors also showed excellent affinity for several galectins (Kd in the low nM range). Despite their high affinity for galectins, 3,3'-derivatized thiodigalactosides still suffer from the drawback of their multi-step synthesis, which involves a double inversion reaction to reach the 3-N-derivatized galactose building block. Furthermore, cyclohexane substitution of one galactose ring in thiodigalactosides has been shown to mimic the galactose ring and thus provide galectin-1 and -3 inhibitors with efficiencies approaching those of diamide- and ditriazolyl-thiodigalactoside derivatives (WO 2010 / 126435). Replacing the D-galactopyranose unit with a substituted cyclohexane reduces polarity and presumably reduces metabolic susceptibility, thus improving drug-like properties.

[0026] Some of the previously described compounds have the general formula: Described in International Publication No. 2005 / 113568 [ka] and Described in International Publication No. 2005 / 113569 [ka] (In the formula, R I can be D-galactose).

[0027] Recently published (T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285) states: [ka] TDG substituted with thiophenetriazole substituents at the C3 and C3' positions with high affinity (<10 nM) for galectin-1 has been disclosed.

[0028] Recently published U.S. Patent Application Publication No. 20140099319, International Publication No. 2014067986, and T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285, Fluorine (F) is present at the meta-position on both phenyl rings relative to the triazole ring. [ka] This compound has been shown to be a promising drug candidate for pulmonary fibrosis, and is particularly highly selective for galectin-3 with high affinity.

[0029] A series of small C1 or C1 and C3 substituted galactopyranosides have been described that show affinity for galectin-3 and 1. β-D-galactopyranoside is reported to have an affinity in the same range as or lower than lactose, with a Kd of approximately 91 μM for galectin-3 and 190 μM for galectin-1 (Giguere, D et al. 2011, 2008, 2006). [ka] The corresponding α-anomers, which have better affinity for galectin-1 or galectin-3 than lactose, are not disclosed or mentioned. Summary of the Invention

[0030] The compounds of the present invention are novel α-D-galactopyranose compounds that unexpectedly exhibit high affinity for galectin-1, and some compounds also have high affinity for galectin-3, making them potential novel drug candidates. Some compounds have excellent systemic uptake in in vitro and in vivo ADME studies, making them suitable for oral treatment of the diseases and disorders disclosed herein.

[0031] In a broad aspect, the present invention provides a D-galactopyranose compound of formula (1): [ka] (In the formula, The pyranose ring is α-D-galactopyranose, A 1 teeth, [ka] and [ka] (wherein, an asterisk * represents the carbon atom of the heteroaromatic ring covalently bonded to the triazole group of formula (1); R 2 is hydrogen, C 1~6 selected from the group consisting of alkyl, OH and halogen; R 3 is hydrogen, C 1~6 selected from the group consisting of alkyl and halogen; R 4is selected from the group consisting of OH, halogen and amino; R 5 is hydrogen, C 1~6 selected from the group consisting of alkyl and halogen selected from the group consisting of: X is S, SO, SO2, O, C=O and CR 2a R 3a Selected from R 2a and R 3a are independently selected from hydrogen, OH, or halogen; B 1 are a) CN, halogen, methyl optionally substituted with F, OCH optionally substituted with F, OCHCH optionally substituted with F, OH and R 4a -CONH-(wherein, R 4a is C 1~3 C substituted with a 5- or 6-membered heteroaromatic ring optionally substituted with a substituent selected from alkyl and cyclopropyl 1~6 Alkyl or branched C 3~6 alkyl; or CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 5a -CONH-(wherein, R 5a is C 1~3 C substituted with phenyl optionally substituted with a substituent selected from alkyl and cyclopropyl 1~6 Alkyl; b) halogen; spiroheterocycles, such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; C2-alkynyl; CN; -COOH; COOC 1~4 Alkyl;-CONR 6 R 7 (In the formula, R 6 and R 7 is H, C 1~3 independently selected from alkyl, cyclopropyl, and isopropyl, or R 6 and R 7 together with the nitrogen form a heterocycloalkyl; C optionally substituted with F 1~3Alkyl; Cyclopropyl optionally substituted with F; Isopropyl optionally substituted with F; SC optionally substituted with F 1~3 Alkyl; OC optionally substituted with F 1~3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8 R 9 (In the formula, R 8 and R 9 is H, C 1~3 independently selected from alkyl and isopropyl; OH; and R 10 -CONH-(wherein, R 10 is C 1~3 alkyl and cyclopropyl); aryl; and heterocycle, for example phenyl or naphthyl; c) halogen, C2-alkynyl, CN, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 11 -CONH-(wherein, R 11 is C 1~3 C optionally substituted with a substituent selected from alkyl and cyclopropyl 5~7 cycloalkyl; and d) halogen; spiroheterocycles, such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; CN; -COOH; COOC 1~4 Alkyl;-CONR 12 R 13 (In the formula, R 12 and R 13 is H, C 1~3 independently selected from alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 together with the nitrogen form a heterocycloalkyl; C optionally substituted with F 1~3 Alkyl; Cyclopropyl optionally substituted with F; Isopropyl optionally substituted with F; SC optionally substituted with F 1~3 Alkyl; OC optionally substituted with F 1~3Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; SC optionally substituted with F 1~3 Alkyl;NR 14 R 15 (In the formula, R 14 and R 15 is H, C 1~3 independently selected from alkyl and isopropyl; OH; aryl; heterocycle; and R 16 -CONH-(wherein, R 16 is C 1~3 e) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from C 1~6 Alkyl or branched C 3~6 Alkyl;f)C 2~6 alkynyl; R 1 is a) H, b) OH, c) phenyl substituted with one or more groups selected from one or more halogens, phenyl, OH and halogens, CN, OR 17 , N.R. 18 R 19 and CONH2 (wherein R 17 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 20 -CONH-(wherein, R 20 is C 1~3 alkyl and cyclopropyl; R 18 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 21 -CONH-(wherein, R 21 is C 1~3 alkyl and cyclopropyl; R 19 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 22-CONH-(wherein, R 22 is C 1~3 OC optionally substituted with alkyl, cyclopropyl, and cyclopropyl. 1~6 alkyl, d) one or more halogens, CN, OR 23 , N.R. 24 R 25 and CONH2 (wherein R 23 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 26 -CONH-(wherein, R 26 is C 1~3 alkyl and cyclopropyl; R 24 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 27 -CONH-(wherein, R 27 is C 1~3 alkyl and cyclopropyl; R 25 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 28 -CONH-(wherein, R 28 is C 1~3 branched OC optionally substituted with alkyl, cyclopropyl, and 3~6 alkyl, and e) one or more halogens, CN, OR 29 , N.R. 30 R 31 and CONH2 (wherein R 29 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 32 -CONH-(wherein, R 32 is C 1~3 alkyl and cyclopropyl; R 30is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 33 -CONH-(wherein, R 33 is C 1~3 alkyl and cyclopropyl; R 31 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 34 -CONH-(wherein, R 34 is C 1~3 a cyclic OC optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl 3~6 alkyl) or a pharmaceutically acceptable salt or solvate thereof.

[0032] In a further aspect, the present invention provides a D-galactopyranose compound of formula (1): [ka] (In the formula, The pyranose ring is α-D-galactopyranose, A 1 teeth, [ka] and [ka] (wherein, an asterisk * represents the carbon atom of the heteroaromatic ring covalently bonded to the triazole group of formula (1); R 2 is hydrogen, C 1~6 selected from the group consisting of alkyl, OH and halogen; R 3 is hydrogen, C 1~6selected from the group consisting of alkyl and halogen; R 4 is selected from the group consisting of OH, halogen and amino; R 5 is hydrogen, C 1~6 selected from the group consisting of alkyl and halogen selected from the group consisting of: X is S, SO, SO2, O, C=O and CR 2a R 3a Selected from R 2a and R 3a are independently selected from hydrogen, OH, or halogen; B 1 are a) CN, halogen, methyl optionally substituted with F, OCH optionally substituted with F, OCHCH optionally substituted with F, OH and R 4a -CONH-(wherein, R 4a is C 1~3 C substituted with a 5- or 6-membered heteroaromatic ring optionally substituted with a substituent selected from alkyl and cyclopropyl 1~6 Alkyl or branched C 3~6 alkyl; or CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 5a -CONH-(wherein, R 5a is C 1~3 C substituted with phenyl optionally substituted with a substituent selected from alkyl and cyclopropyl 1~6 Alkyl; b) halogen; CN; -COOH; -CONR 6 R 7 (In the formula, R 6 and R 7 is H, C 1~3 independently selected from alkyl, cyclopropyl, and isopropyl, or R 6 and R 7 together with the nitrogen form a heterocycloalkyl; C optionally substituted with F 1~3Alkyl; Cyclopropyl optionally substituted with F; Isopropyl optionally substituted with F; OC optionally substituted with F 1~3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8 R 9 (In the formula, R 8 and R 9 is H, C 1~3 independently selected from alkyl and isopropyl; OH; heterocycle; and R 10 -CONH-(wherein, R 10 is C 1~3 alkyl and cyclopropyl), e.g., phenyl or naphthyl; c) halogen, C2-alkynyl, CN, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 11 -CONH-(wherein, R 11 is C 1~3 C optionally substituted with a substituent selected from alkyl and cyclopropyl 5~7 cycloalkyl; and d) halogen; spiroheterocycles, such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; CN; -COOH; -CONR 12 R 13 (In the formula, R 12 and R 13 is H, C 1~3 independently selected from alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 together with the nitrogen form a heterocycloalkyl; C optionally substituted with F 1~3 Alkyl; Cyclopropyl optionally substituted with F; Isopropyl optionally substituted with F; OC optionally substituted with F 1~3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14 R 15 (In the formula, R 14 and R 15is H, C 1~3 independently selected from alkyl and isopropyl; OH; heterocycle; and R 16 -CONH-(wherein, R 16 is C 1~3 e) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from C 1~6 Alkyl or branched C 3~6 Alkyl;f)C 2~6 alkynyl, R 1 is a) H, b) OH, c) phenyl substituted with one or more groups selected from one or more halogens, phenyl, OH and halogens, CN, OR 17 , N.R. 18 R 19 and CONH2 (wherein R 17 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 20 -CONH-(wherein, R 20 is C 1~3 alkyl and cyclopropyl; R 18 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 21 -CONH-(wherein, R 21 is C 1~3 alkyl and cyclopropyl; R 19 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 22 -CONH-(wherein, R 22 is C 1~3 OC optionally substituted with alkyl, cyclopropyl, and cyclopropyl. 1~6 alkyl, d) one or more halogens, CN, OR 23 , N.R. 24 R25 and CONH2 (wherein R 23 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 26 -CONH-(wherein, R 26 is C 1~3 alkyl and cyclopropyl; R 24 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 27 -CONH-(wherein, R 27 is C 1~3 alkyl and cyclopropyl; R 25 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 28 -CONH-(wherein, R 28 is C 1~3 branched OC optionally substituted with alkyl, cyclopropyl, and 3~6 alkyl, and e) one or more halogens, CN, OR 29 , N.R. 30 R 31 and CONH2 (wherein R 29 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 32 -CONH-(wherein, R 32 is C 1~3 alkyl and cyclopropyl; R 30 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 33 -CONH-(wherein, R 33 is C 1~3 alkyl and cyclopropyl; R31 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 34 -CONH-(wherein, R 34 is C 1~3 a cyclic OC optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl 3~6 alkyl) or a pharmaceutically acceptable salt or solvate thereof.

[0033] In one embodiment, B 1 d) halogen; spiroheterocycles, such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; CN; -COOH; -CONR 12 R 13 (In the formula, R 12 and R 13 is H, C 1~3 C optionally substituted with F; 1~3 Alkyl; Cyclopropyl optionally substituted with F; Isopropyl optionally substituted with F; OC optionally substituted with F 1~3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14 R 15 (In the formula, R 14 and R 15 is H, C 1~3 independently selected from alkyl and isopropyl; OH; heterocycle; and R 16 -CONH-(wherein, R 16 is C 1~3 Heterocycle optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl, for example heteroaryl or heterocycloalkyl.

[0034] In one embodiment, A 1 is R 2 is selected from the group consisting of hydrogen, methyl, OH, and halogen; R3 is hydrogen, C 1~6 In a preferred embodiment, R is selected from the group consisting of alkyl and halogen. 2 is hydrogen, methyl or halogen, and R 3 is H. Depending on the conditions, such as acidic or basic, the OH group may be in the oxo tautomeric form. In another preferred embodiment, R 2 is a halogen and R 3 is hydrogen. In a further embodiment, R 2 is a halogen, for example Cl; R 3 is C 1~6 It is selected from the group consisting of alkyl, such as methyl, and halogen, such as Cl.

[0035] In yet a further embodiment, A 1 is R 4 is selected from the group consisting of OH, halogen, and amino; R 5 is hydrogen, C 1~6 In a preferred embodiment, R is selected from the group consisting of alkyl and halogen. 4 is OH and R 5 is hydrogen. In another preferred embodiment, R 4 is amino and R 5 is hydrogen. In a further preferred embodiment, R 4 is a halogen and R 5 is hydrogen.

[0036] In a preferred embodiment, A 1 teeth [ka] is.

[0037] In a further embodiment, A 1 teeth [ka] is.

[0038] In another preferred embodiment, A 1 teeth [ka] and R 1 is selected from the group consisting of a), c), d) and e) of the above embodiments.

[0039] In an even more preferred embodiment, A 1 teeth [ka] is.

[0040] In a further preferred embodiment, A 1 teeth [ka] and R 1 is selected from the group consisting of a), c), d) and e) of the above embodiments.

[0041] In an even more preferred embodiment, A 1 teeth [ka] and R 1 is selected from the group consisting of a), c), d) and e) of the above embodiments.

[0042] In a further embodiment, A 1 teeth [ka] is.

[0043] In yet a further embodiment, A 1 teeth [ka] is.

[0044] In a further embodiment, X is selected from S, SO, SO2 and O, such as S, SO and SO2, preferably S.

[0045] In still further embodiments, R 1 H, OH, OC 1~4 OC substituted with at least one group from the group consisting of alkyl, such as O-methyl, O-ethyl or O-isopropyl, phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1~4 In a more preferred embodiment, R 1 H,OC 1~4 OC substituted with at least one group from the group consisting of alkyl, such as O-methyl, O-ethyl or O-isopropyl, phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1~4 In an even more preferred embodiment, R 1 is O.C. 1~4 OC substituted with at least one group from the group consisting of alkyl, such as O-methyl, O-ethyl or O-isopropyl, phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1~4 alkyl.

[0046] In another embodiment, R 1 is H, OH, OCH3, and OC optionally substituted with one or more halogens 1~6 Alkyl; for example, selected from H, OH, OCH3, and OCH2CF3.

[0047] In a further embodiment, B 1is selected from halogen; C2-alkynyl; CN; methyl optionally substituted with F; and heteroaryl optionally substituted with a group selected from heteroaryl. In a further embodiment, B1 is selected from halogen; CN; methyl optionally substituted with F; and heteroaryl optionally substituted with a group selected from heteroaryl. Preferably, B1 is selected from Cl; Br; CN; ethynyl; methyl; CF3; pyridine; pyrimidine; oxazole; and pyridinyl optionally substituted with a group selected from thiazole.

[0048] In still further embodiments, B1 is selected from the group consisting of halogen, C2-alkynyl, CN, methyl optionally substituted with F, spiroheterocycle, and SC optionally substituted with F. 1~3 Alkyl;CONR 12 R 13 (In the formula, R 12 and R 13 is H, C 1~3 independently selected from alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 together with the nitrogen form a heterocycloalkyl); and heteroaryl optionally substituted with a group selected from a heterocycle, such as tetrahydropyridine.

[0049] In a further embodiment, B1 is selected from Cl; Br; F; ethynyl; N-(2-oxa)-6-azaspiro[3.3]heptanyl; CO-azetidinyl; CONHCH3; CONHCH2CH3; CON(CH3)2; CN; methyl; SCH3; SCF3; CF3; imidazole; pyridine; pyrimidine; oxazole; and pyridinyl optionally substituted with a group selected from thiazole.

[0050] In a further embodiment, B1 is selected from pyridinyl substituted with one or more groups selected from Cl, Br and CN. Typically, B1 is selected from pyridinyl substituted with one, two or three, for example one or two, groups selected from Cl, Br and CN.

[0051] In yet a further embodiment, B 1 is selected from heterocycloalkyl, such as tetrahydrobipyridine.

[0052] In a further embodiment, B 1 is a spiro heterocycle; CONR 12 R 13 (In the formula, R 12 and R 13 is H, C 1~3 independently selected from alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 together with the nitrogen form a heterocycloalkyl). Typically, B1 is selected from pyridinyl optionally substituted with a group selected from N-(2-oxa)-6-azaspiro[3.3]heptanyl; CO-azetidinyl; CONHCH3; CONHCH2CH3; CON(CH3)2; and imidazole.

[0053] In still further embodiments, B1 is selected from benzothiazolyl or thiazolepyridyl optionally substituted with a group selected from Cl; Br; F; ethynyl; N-(2-oxa)-6-azaspiro[3.3]heptanyl; CO-azetidinyl; CONHCH3; CONHCH2CH3; CON(CH3)2; CN; methyl; SCH3; SCF3; CF3; imidazole; pyridine; pyrimidine; oxazole; and thiazole.

[0054] In a further embodiment, B 1 is halogen; and C optionally substituted with F 1~3 phenyl optionally substituted with a group selected from alkyl.

[0055] In yet a further embodiment, B 1 CN;-CONR 6 R 7 (In the formula, R 6 and R7 is H, C 1~3 phenyl optionally substituted with a group selected from alkyl, cyclopropyl and isopropyl. Typically, B 1 is selected from phenyl optionally substituted with a group selected from CN and CONHCH3.

[0056] In a further embodiment, B1 is halogen; CN; -CONR 6 R 7 (In the formula, R 6 and R 7 is H, C 1~3 alkyl, cyclopropyl, and isopropyl; and C optionally substituted with F 1~3 phenyl optionally substituted with a group selected from alkyl.

[0057] In still further embodiments, B1 is selected from the group consisting of Cl; F; Br; CN; CONHCH3; and C optionally substituted with F. 1~3 phenyl optionally substituted with a group selected from alkyl.

[0058] In yet further embodiments, B1 is selected from phenyl substituted with a group selected from Cl, F and methyl. Typically, B1 is selected from phenyl substituted with one, two or three, for example one or two, selected from Cl, F and methyl.

[0059] In still further embodiments, the compound of formula (1) is 3,5-dichloro-4-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 2-O-benzyl-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-6-cyano-3-pyridyl 3-deoxy-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-6-cyanopyridin-3-yl 3-deoxy-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyrimidin-5-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-1',2',3',6'-tetrahydro[2,4'-bipyridin]-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(thiazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-4-(trifluoromethyl)phenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-Bromo-6-trifluoromethylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside; or a pharmaceutically acceptable salt or solvate thereof is selected from one of the following.

[0060] In a further embodiment, the compound of formula (1) is 3,5-dichloro-4-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 2-O-benzyl-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-bromo-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyrimidin-5-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(thiazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-4-(trifluoromethyl)phenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3-bromo-2-trifluoromethylpyridin-5-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-deoxy-3-[4-(4-methyltriazol-2-yl)-1H-1,2,3-thiazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptanyl}pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside, 3-cyano-2-(trifluoromethyl)pyridin-5-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-azetidinylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3-chloro-5-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4,5-dichlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-(N-methylcarbonyl)phenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 2,5-dichlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-chlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-fluorophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-ethyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-2-O-(2,2,2-trifluoroethyl)-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-(N,N-dimethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-ethynyl-2-(N,N-dimethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynyl-2-(N-azetidinylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-ethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside; 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 1,3-Benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 1,3-Benzothiazol-6-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 1,3-Benzothiazol-6-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyano-1,3-benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, Thiazolo[4,5-b]pyridin-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-Methylsulfanylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, and 5-(Trifluoromethylsulfanyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside; or a pharmaceutically acceptable salt or solvate thereof is selected from one of the following.

[0061] In a further aspect, the present invention relates to a compound of formula (1) for use as a medicament.

[0062] In a still further aspect, the present invention relates to a pharmaceutical composition comprising a compound according to any one of the preceding claims and optionally pharmaceutically acceptable additives, such as carriers and / or excipients.

[0063] In a further aspect, the present invention relates to a compound of formula (1) of the present invention for use in a method for treating a disorder associated with the binding of galectin-1 and / or galectin-3 to its ligand in a mammal, e.g., a human. In a further embodiment, the disorder is selected from the group consisting of inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndromes; fibrosis, e.g., pulmonary fibrosis, liver fibrosis, renal fibrosis, ocular fibrosis, and cutaneous and cardiac fibrosis; focal fibrosis, e.g., Dupuytren's disease and Peyronie's disease; fibrotic complications of other treatments, e.g., coronary artery stents, biliary stents, cerebral artery stents, ureteral stents; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonia; abnormal scar formation; surgical adhesions. ;septic shock;cancer, e.g., colorectal cancer, other gastrointestinal cancers, e.g., pancreatic cancer, stomach cancer, biliary tract cancer, lung cancer, mesothelioma, female cancers, e.g., breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube (salpingo) cancer, brain cancer, e.g., medulloblastoma, glioma, meningioma, bone and muscle sarcoma and other sarcomas, leukemia and lymphoma, e.g., T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven bone disease autoimmune diseases, such as psoriasis, rheumatoid arthritis, rheumatoid lung; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections, such as influenza virus, HIV, herpes virus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or diseases or conditions associated with ocular angiogenesis, such as neovascularization associated with cancer; and ocular diseases, such as age-related macular degeneration and corneal The disease is selected from the group consisting of neovascularization; atherosclerosis; metabolic disease; diabetes; type 1 diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Loeys-Dietz syndrome; nephropathy; diastolic HF; fibrotic pulmonary complications of aPD1 and other CPI treatment; asthma and other interstitial lung diseases (including Hermansky-Pudlak syndrome), liver disorders such as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease; uterine diseases such as uterine fibroids and uterine or cervical fibrosis.

[0064] In a still further aspect, the present invention relates to a method for treating a disorder associated with the binding of galectin-1 and / or galectin-3 to its ligand in a mammal, e.g., a human, comprising administering a therapeutically effective amount of at least one compound of formula (1) of the present invention to a mammal in need of said treatment. In a further embodiment, the disorder is selected from the group consisting of inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndromes; fibrosis, e.g., pulmonary fibrosis, liver fibrosis, renal fibrosis, ocular fibrosis, and cutaneous and cardiac fibrosis; focal fibrosis, e.g., Dupuytren's disease and Peyronie's disease; fibrotic complications of other treatments, e.g., coronary artery stents, biliary stents, cerebral artery stents, ureteral stents; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonia; abnormal scar formation; surgical adhesions. ;septic shock;cancer, e.g., colorectal cancer, other gastrointestinal cancers, e.g., pancreatic cancer, stomach cancer, biliary tract cancer, lung cancer, mesothelioma, female cancers, e.g., breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube (salpingo) cancer, brain cancer, e.g., medulloblastoma, glioma, meningioma, bone and muscle sarcoma and other sarcomas, leukemia and lymphoma, e.g., T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven bone disease autoimmune diseases, such as psoriasis, rheumatoid arthritis, rheumatoid lung; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections, such as influenza virus, HIV, herpes virus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or diseases or conditions associated with ocular angiogenesis, such as neovascularization associated with cancer; and ocular diseases, such as age-related macular degeneration and corneal The disease is selected from the group consisting of neovascularization; atherosclerosis; metabolic disease; diabetes; type 1 diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Loeys-Dietz syndrome; nephropathy; diastolic HF; fibrotic pulmonary complications of aPD1 and other CPI treatment; asthma and other interstitial lung diseases (including Hermansky-Pudlak syndrome), liver disorders such as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease; uterine diseases such as uterine fibroids and uterine or cervical fibrosis.

[0065] Another aspect of the present invention relates to combination therapy comprising administering a compound of formula (I) of the present invention together with a therapeutically active compound that is different from the compound of formula (I) (interchangeably a "different therapeutically active compound"). In one embodiment, the present invention relates to a combination of a compound of formula (I) with a different therapeutically active compound for use in treating a disorder associated with the binding of galectin-1 and / or galectin-3 to its ligand in a mammal. Such disorders are disclosed below.

[0066] In one embodiment of the present invention, a therapeutically effective amount of at least one compound of formula (I) of the present invention is administered in combination with a different therapeutically active compound to a mammal in need thereof. In a further embodiment, the combination of a compound of formula (I) with a different therapeutically active compound is used to treat inflammation; fibrosis, such as pulmonary fibrosis, liver fibrosis, kidney fibrosis, ocular fibrosis, and fibrosis of the skin and heart; scarring; keloid formation; abnormal scar formation; surgical adhesions; septic shock; cancer, such as carcinoma, sarcoma, leukemia and lymphoma, including T-cell lymphoma; metastatic cancer; autoimmune diseases, such as psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; metabolic disorders; heart disease; heart failure; pathological vascular The compound is administered to a mammal suffering from a disorder selected from the group consisting of neovascularization, e.g., ocular neovascularization or a disease or condition associated with ocular neovascularization, e.g., neovascularization associated with cancer; and ocular diseases, e.g., age-related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases, e.g., diabetes; type 2 diabetes; insulin resistance; obesity; diastolic heart failure; asthma and other interstitial lung diseases, including Hermansky-Pudlak syndrome and mesothelioma; and liver disorders, e.g., non-alcoholic steatohepatitis or non-alcoholic fatty liver disease.

[0067] Exemplary, non-limiting groups of cancers that may be treated, managed, and / or prevented by administration of a compound of Formula (I) in combination with a different therapeutically active compound include colon cancer, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endothelial sarcoma, lymphangiosarcoma, lymphangioendothelial sarcoma, and leukocyte sarcoma. sarcoma), synovium, mesothelioma, Ewing's sarcoma, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, cholangiocarcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung cancer, small cell lung cancer, bladder cancer, epithelial carcinoma, glioblastoma, neuroma, craniopharyngioma, schwannoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, medulloblastoma Meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia and lymphoma, acute lymphocytic leukemia and acute myelocytic polycythemia vera, multiple myeloma, Waldenstrom's macroglobulinemia and heavy chain disease, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, rectal cancer, urinary tract cancer, uterine cancer, oral cancer, skin cancer, stomach cancer, brain cancer, liver cancer, laryngeal cancer, esophageal cancer, breast tumors, childhood null acute lymphoblastic leukemia (ALL), thymic ALL, B-cell ALL, acute myeloid leukemia, myelomonocytic leukemia (MYELOCYTOID ALL) leukemia), acute megakaryocytic leukemia, Burkitt's lymphoma, acute myeloid leukemia, chronic myeloid leukemia, and T-cell leukemia, small and large non-small cell lung cancer, acute granulocytic leukemia, germ cell tumors, endometrial cancer, gastric cancer, head and neck cancer, chronic lymphocytic leukemia, hairy cell leukemia, and thyroid cancer.

[0068] In some embodiments of the present invention, the administration of at least one compound of formula (I) of the present invention and at least one additional therapeutic agent exhibits therapeutic synergy. In some embodiments of the methods of the present invention, the measured response to treatment observed after administering both at least one compound of formula (I) of the present invention and the additional therapeutic agent is improved compared to the same measured response to treatment observed after administering either at least one compound of formula (I) of the present invention or the additional therapeutic agent alone.

[0069] A further aspect of the present invention relates to a combination therapy comprising administering a compound of formula (I) of the present invention together with an antifibrotic compound different from the compound of formula (I) to a mammal in need thereof. In a further embodiment, such an antifibrotic compound may be selected from the following non-limiting group of antifibrotic compounds: pirfenidone, nintedanib, sintuzumab (GS-6624, AB0024), BG00011 (STX100), PRM-151, PRM-167, PEG-FGF21, BMS-986020, FG-3019, MN-001, IW001, SAR156597, GSK2126458, PAT-1251, and PBI-4050.

[0070] A still further aspect of the present invention relates to a combination therapy comprising administering a compound of formula (I) to a mammal in need thereof in combination with chemotherapy or radiation therapy, or further conventional cancer treatments such as immunostimulant therapy, gene therapy, antibody therapy and dendritic cell-based therapy, or mRNA-based therapy (including mRNA-based cancer vaccines), and / or viral-based cancer vaccines.

[0071] In one embodiment, the compound of formula (I) is administered with at least one additional therapeutic agent selected from anti-neoplastic chemotherapeutic agents. In further embodiments, the antineoplastic chemotherapeutic agent is selected from all-trans retinoic acid, actimid, azacitidine, azathioprine, bleomycin, carboplatin, capecitabine, cisplatin, chlorambucil, cyclophosphamide, cytarabine, daunorubicin, docetaxel, doxifluridine, doxorubicin, epirubicin, etoposide, fludarabine, fluorouracil, gemcitabine, hydroxyurea, idarubicin, irinotecan, lenalidomide, leucovorin, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, revlimid, temozolomide, teniposide, thioguanine, valrubicin, vinblastine, vincristine, vindesine, and vinorelbine. In one embodiment, the chemotherapeutic agent used in this combination of drugs may itself be a combination of different chemotherapeutic agents.Suitable combinations include FOLFOX and IFL.FOLFOX is a combination that includes 5-fluorouracil (5-FU), leucovorin, and oxaliplatin.IFL treatment includes irinotecan, 5-FU, and leucovorin.

[0072] In further embodiments of the invention, the additional conventional cancer treatment comprises radiation therapy. In some embodiments, the radiation therapy comprises local radiation therapy delivered to the tumor. In some embodiments, the radiation therapy comprises total body irradiation.

[0073] In another embodiment of the present invention, the additional cancer treatment is an immunostimulatory substance, such as a cytokine or an antibody. Such cytokines may be selected from the group consisting of, but not limited to, GM-CSF, type I IFN, interleukin-21, interleukin-2, interleukin-12, and interleukin-15. The antibody is preferably an immunostimulatory antibody, such as an anti-CD40 antibody or an anti-CTLA-4 antibody. The immunostimulatory substance may also be a substance capable of depleting immunosuppressive cells (e.g., regulatory T cells) or factors, such as an E3 ubiquitin ligase. E3 ubiquitin ligases (HECT, RING, and U-box proteins) have emerged as important molecular regulators of immune cell function and may be involved in regulating the immune response during infection by targeting specific inhibitory molecules for proteolytic destruction, respectively. Several HECT and RING E3 proteins have also now been implicated in the induction and maintenance of immune self-tolerance: c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4 negatively regulate T cell growth factor production and proliferation, respectively.

[0074] In some embodiments of the present invention, the compound of formula (I) is administered with at least one additional therapeutic agent selected from checkpoint inhibitors. In some embodiments of the present invention, the checkpoint inhibitor acts on one or more of the following non-limiting targets: CEACAM1, galectin-9, TIM3, CD80, CTLA4, PD-1, PD-L1, HVEM, BTLA, CD160, VISTA, B7-H4, B7-2, CD155, CD226, TIGIT, CD96, LAG3, GITF, OX40, CD137, CD40, IDO, and TDO, kynurenine antagonists. These are known targets, and some of these targets are described in Melero et al., Nature Reviews Cancer (2015). Examples of checkpoint inhibitors administered with compounds of formula (1) are anti-PD-1: nivolumab, pembrolizumab, cemiplimab, anti-PD-L1: atezolizumab, avelumab, durvalumab, and one anti-CTLA-4: ipilimumab. Each of these checkpoint inhibitors can be the subject of an embodiment in combination with any one of the compounds of formula (1).

[0075] In some embodiments of the present invention, the compound of Formula (I) is administered with at least one additional therapeutic agent selected from inhibitors of indoleamine-2,3-dioxygenase (IDO).

[0076] In some embodiments of the present invention, the compound of Formula (I) is administered with at least one additional therapeutic agent selected from one or more inhibitors of the CTLA4 pathway, hi some embodiments, the inhibitors of the CTLA4 pathway are selected from one or more antibodies to CTLA4.

[0077] In some embodiments of the invention, the compound of Formula (I) is administered with at least one additional therapeutic agent selected from one or more inhibitors of the PD-1 / PD-L pathway. In some embodiments, the one or more inhibitors of the PD-1 / PD-L pathway are selected from one or more antibodies or antibody fragments against PD-1, PD-L1 and / or PD-L2, or other methods capable of inducing anti-PD1 antibodies, such as mRNA-based transfer of genetic material directing the endogenous production of anti-PD1 or anti-PDL1 antibodies or fragments of such antibodies.

[0078] In yet a further aspect, the present invention provides a method for preparing a compound of formula II or a pharmaceutically acceptable salt or solvate thereof, comprising step a1 (wherein A 1 , B 1 and R 1 is defined above in Equation 1); [ka] a1) a compound of formula I, wherein X 1 and X 2 together form a protecting group such as benzylidene) in the presence of an acid such as TFA in an inert organic solvent such as DCM, followed by neutralization with a base such as triethylamine, optionally at a temperature below room temperature, to provide a compound of formula II; optionally, a compound of formula 1 (wherein X 1 and X 2 are two protecting groups such as acetate) in an organic solvent such as methanol, optionally in the presence of water, in the presence of a base such as triethylamine, sodium hydroxide or sodium methoxide, followed by neutralization using an acid such as HCl to provide a compound of formula II.

[0079] In yet a further aspect, the present invention provides a method for preparing a compound of formula II or a pharmaceutically acceptable salt or solvate thereof, comprising step a2 (wherein A 1 and B 1 is defined above in Equation 1); [ka] a2) a compound of formula III, wherein X 3 and X 4 is hydrogen or a protecting group, e.g., acetate), optionally at elevated temperature, optionally in the presence of a catalyst such as oxotrichloro[(dimethylsulfide)triphenylphosphineoxide]rhenium(V) or BF3OEt2, in an organic solvent such as toluene, to form a compound of formula B 1 -SH to give a compound of formula IV; X 3 and X 4 If is a protecting group such as acetate, then this could be removed in an additional step in the presence of a base such as triethylamine, LiOH or sodium methoxide in a suitable solvent such as methanol and water to give compounds of formula IV.

[0080] In yet a further aspect, the present invention provides a method for preparing a compound of formula II or a pharmaceutically acceptable salt or solvate thereof, comprising step a3 (wherein A 1 , B 1 and R 1 is defined above in Equation 1); [ka] a3) reacting a compound of formula V with a compound of formula A in an inert solvent such as DMF or acetonitrile using a base such as diisopropylethylamine or L-ascorbic acid sodium salt, catalyzed by a copper salt such as CuI or copper(II) sulfate, optionally using a reagent such as CsF 1 -CC-H or A 1 -CC-TMS to give the compound of formula II.

[0081] In yet a further aspect, the present invention provides a method for preparing a compound of formula VIII or a pharmaceutically acceptable salt or solvate thereof, comprising steps a4-a5, 1 and B1 is defined above in Equation 1); [ka] a4) reacting a compound of formula VI with a compound of formula X, optionally in the presence of a reagent such as NaH, CsCO or AgO, in an organic solvent such as DMF 3 -L 1 wherein X 3 together with O to form an OX in formula 1 selected from c) of the definition of R1 above. 3 And L 1 is reacted with a leaving group, for example a halide such as Cl, Br, I, or a sulfate such as mesylate, tosylate, or triflate, to provide a compound of formula VII. a5) reacting a compound of formula VII with a compound of formula A in an inert solvent such as DMF or acetonitrile using a base such as diisopropylethylamine or L-ascorbic acid sodium salt, catalyzed by a copper salt such as CuI or copper(II) sulfate, optionally with a reagent such as CsF 1 -CC-H or A 1 -CC-TMS to give a compound of formula VIII.

[0082] In yet a further aspect, the present invention provides a method for preparing a compound of formula VIII or a pharmaceutically acceptable salt or solvate thereof, comprising steps a6-a7, 1 , B 1 and R 1 is defined above in Equation 1); [ka] a6) reacting a compound of formula IX with a compound of formula A in an inert solvent such as DMF or acetonitrile using a base such as diisopropylethylamine or L-ascorbic acid sodium salt, catalyzed by a copper salt such as CuI or copper(II) sulfate, optionally using a reagent such as CsF 1 -CC-H or A 1-CC-TMS to give a compound of formula X. a7) reacting a compound of formula X with a compound of formula X, optionally in the presence of a reagent such as NaH, CsCO or AgO, in an organic solvent such as DMF 3 -L 1 wherein X 3 together with O to form an OX in formula 1 selected from c) of the definition of R1 above. 3 And L 1 is defined as a leaving group, for example a halide such as Cl, Br, I, or a sulfate such as mesylate, tosylate, or triflate, to provide a compound of formula VIII.

[0083] In yet a further aspect, the present invention provides a method for preparing a compound of formula XII or a pharmaceutically acceptable salt or solvate thereof, comprising step a8 (wherein A 1 , B 1 and R 1 is defined above in Equation 1); [ka] a8) a compound of formula XI, wherein B 2 is B in sections b) and d) of Equation 1 1 Selected from L 3 is defined as a halide such as I, Br or Cl) with a metallo-organic compound such as Zn(CN) in the presence of Zn and 1,1'-bis(diphenylphosphino)ferrocene and Pd(dba) in a suitable organic solvent such as DMF, optionally at elevated temperature, to give a compound of formula XII, where X 6 is defined as —CN) to give a compound of formula XI, optionally as defined above, by reacting with a borinane, such as 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane, in the presence of an organometallic catalyst, such as Pd(PPh4)3, and an inorganic base, such as K2CO3, in a suitable solvent, such as 1,4-dioxane, optionally at elevated temperature, to give a compound of formula XII, 6is defined as methyl) to give a compound of formula XII, optionally by reacting a compound of formula XI as defined above with a stannane, such as tributyl(oxazol-2-yl)stannane or tributyl(thiazol-2-yl)stannane, optionally in the presence of an organometallic catalyst, such as Pd(PPh3)4, optionally at elevated temperature, in the presence of CsF, to give a compound of formula XII, 6 is an optionally substituted 5- or 6-membered heteroaromatic ring; optionally reacting a compound of formula XI as defined above with a heterocyclic borinate, such as tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate, in the presence of a catalyst, such as bis(triphenylphosphine)palladium(II) chloride, in an organic solvent, such as 1,4-dioxane, optionally in the presence of water, and optionally in the presence of a base, such as potassium carbonate, optionally at elevated temperature, to give a compound of formula XII, wherein X 6 is defined as a 5- or 6-membered heteroaromatic or heterocyclic ring); optionally, the compound of formula XI could be reacted with an alkyne or protected alkyne, such as ethynyl(trimethyl)silane, in the presence of one or more organometallic reagents, such as CuI, bis(triphenylphosphine)palladium(II) chloride, in an inert solvent, such as THF, optionally in the presence of an organic base, such as triethylamine or DIPEA, and optionally at elevated temperatures, such as 30-80°C. If the alkyne reagent is protected with a silyl protecting group, such as trimethylsilane, the protecting group could be removed in a successive step by adding a reagent, such as TBAF or KF.

[0084] In yet a further aspect, the present invention provides a method for preparing a compound of formula III or a pharmaceutically acceptable salt or solvate thereof, comprising steps a9-a10, 1 is defined above in Equation 1, and X 7 and X 8 are optionally independently selected from hydrogen and acetate; [ka] a9) reacting a compound of formula XIII with a compound of formula A in an inert solvent such as DMF or acetonitrile using a base such as diisopropylethylamine or L-ascorbic acid sodium salt, catalyzed by a copper salt such as CuI or copper(II) sulfate, optionally with a reagent such as CsF 1 -CC-H or A 1 -CC-TMS to give a compound of formula XIV. a10) Reacting a compound of formula XIV with HBr and an acid such as acetic acid in an inert solvent such as DCM for 0-10 hours, after which the product is isolated and further reacted in the presence of ammonium chloride and zinc in a solvent such as acetonitrile for 3-7 days to give a compound of formula III.

[0085] In yet a further aspect, the present invention provides a method for preparing a compound of formula XIX or a pharmaceutically acceptable salt or solvate thereof, comprising steps a11 to a14 (wherein A 1 and B 1 is defined above in Equation 1); [ka] a11) Compound XV is reacted with a chlorinating agent, such as dichloromethyl methyl ether or PCl5, in the presence of a Lewis acid, such as BF3Et2O, in an inert solvent, such as dichloromethane or chloroform, to give a compound of formula XVI, where L 2 is defined as chlorine). a12) reacting a compound of formula VII with a compound of formula HS-B in an inert solvent such as DMF in the presence of a base such as sodium hydride 1 to give a compound of formula IX. a13) Reaction of a compound of formula XVII in the presence of a base such as triethylamine, sodium hydroxide or sodium methoxide in an organic solvent such as methanol, optionally in the presence of water, followed by neutralization using an acid such as HCl, gives a compound of formula XVIII. a14) Reaction of a compound of formula XVIII with a reagent such as benzaldehyde dimethyl acetal in the presence of an acid such as D(+)-10-camphorsulfonic acid in an inert solvent such as DMF or toluene, optionally at elevated temperature and optionally under reduced pressure, and distilling off the methanol to give a compound of formula XIX.

[0086] In yet a further aspect, the present invention provides a method for preparing a compound of formula VI or a pharmaceutically acceptable salt or solvate thereof, comprising steps a15 to a20, 1 and B 1 is defined above in Equation 1, and X 9 and X 10 are optionally independently selected from hydrogen and acetate, or taken together to form a protecting group such as benzylidene; [ka] a15) Reaction of a compound of formula XX with a reagent such as benzaldehyde dimethyl acetal in the presence of an acid such as D(+)-10-camphorsulfonic acid in an inert solvent such as DMF or toluene, optionally at elevated temperature and optionally under reduced pressure, and evaporating the methanol to give a compound of formula XXI, where X 9 and X 10 together to form a benzylidene). a16) A compound of formula XXI is reacted with a methylating reagent, such as methyl iodide, in the presence of a base, such as sodium hydride, in an inert solvent, such as DMF, to give a compound of formula XXII. a17) Reacting a compound of formula XXII with acetic anhydride in the presence of an acid such as H2SO4 to give a compound of formula XXIII (wherein X 9 ~X 11 is defined as acetate). a18) Compound XXIII is reacted with a chlorinating reagent, such as dichloromethyl methyl ether or PCl5, in the presence of a Lewis acid, such as BF3Et2O, in an inert solvent, such as dichloromethane or chloroform, to give a compound of formula XXIV. a19) Reaction of a compound of formula XXIV with a thioacetate, such as potassium thioacetate, in an inert solvent, such as DMF, gives a compound of formula XXV. a20) Compound XXV of formula B in an inert solvent such as DMF in the presence of a base such as diethylamine 1 -L 4 (In the formula, L 4 is defined as a leaving group, for example, a fluoride or a sulfate such as a triflate) to provide a compound of formula XXVI.

[0087] In still a further aspect, the present invention provides a compound of formula A 1 -CC-H or A 1 A method for preparing a compound of formula -CC-TMS, comprising the steps of: 1 is defined above in formula (1): a21) Formula A 1 -L 5 wherein L 5 is defined as a leaving group such as chlorine or bromine) is reacted with trimethylsilane-acetylene using a palladium catalyst such as bis(triphenylphosphine)palladium(II) chloride, copper iodide and a base such as diisopropylethylamine in an inert solvent such as tetrahydrofuran (THF) to give the compound of formula A 1 -CC-H or A 1 The compound -CC-TMS is obtained.

[0088] In a still further aspect, the present invention relates to a method for preparing a compound of formula XXVII, comprising steps a22 to a23: [ka] a22) Chloroacetyl chloride is reacted with trimethyl(2-trimethylsilylethynyl)silane in the presence of AlCl3 in an inert solvent such as DCM to give XXVII. a23) A compound of formula XXVII is reacted with thiourea in an inert solvent such as DMF to give a compound of formula XXVIII.

[0089] In a still further aspect, the present invention provides a method for preparing a compound of formula XXXI, comprising steps a24-a25 (wherein B 1 is defined above in equation (1); [ka] a24) Compounds of formula XXIX could be treated with sodium nitrite to form the corresponding diazo compound, which could be further reacted with a sulfurus source such as potassium ethylxanthate to form compounds of formula XXX. a25) Reacting a compound of formula XXX with a base such as potassium hydroxide to give a compound of formula XXXI.

[0090] In a still further aspect, the present invention provides a method for preparing a compound of formula XXXIII, comprising step a26 (wherein B 1 is defined above in equation (1); [ka] a25) A compound of formula XXXII is reacted with Na2S·10H2O in the presence of a base such as NaOH in an inert solvent such as DMF to give a compound of formula XXXIII.

[0091] In a still further aspect, the present invention provides a method for preparing a compound of formula XXXVII, comprising steps a27 to a29, wherein B 1 is defined above in equation (1); [ka] a27) Reaction of a compound of formula XXXIV with an activated thioamide, such as dimethylcarbamoyl chloride, using a base, such as sodium hydride, in an inert solvent, such as DMF, gives a compound of formula XXXV. a28) Heating the compound of formula XXXV at elevated temperature to form compound XXXVI. a29) Reacting a compound of formula XXXVI with a base such as potassium hydroxide to give a compound of formula XXXVII.

[0092] In a still further aspect, the present invention provides a method for preparing a compound of formula XXXIX, comprising step a30 (wherein B 1 is defined above in equation (1); [ka] a30) A compound of formula XXXVIII, where L is a leaving group such as bromine, is reacted with CuCN in an inert solvent such as dimethylformamide, optionally at elevated temperature, to give a compound of formula XXXIX.

[0093] In a still further aspect, the present invention provides a method for preparing a compound of formula XLI, comprising step a31 (wherein B 1 is defined above in equation (1); [ka] a31) a compound of formula XL, wherein B 1 where X is defined above and L is a leaving group such as iodine) is reacted with KF and CuI, optionally at elevated temperature, to give an intermediate which is further reacted with trimethyl(trifluoromethyl)silane to give an intermediate which is dissolved in an inert solvent such as 1-methyl-2-pyrrolidinone (NMP) and 3,5-dichloro-2-iodopyridine is added to give a compound of formula XLI.

[0094] In a still further aspect, the present invention provides a compound of formula V, wherein B 1 and R 1 is defined with respect to formula 1), or a pharmaceutically acceptable salt or solvate thereof, comprising steps a31 and a32; [ka] a32) Reaction of a compound of formula XLII with a sulfurus nucleophile, such as potassium thioacetate, in an inert solvent, such as DMF, gives compound XLVI. a33) Compounds of formula XLVI are reacted with compounds of formula B in an inert solvent such as DMF using a base such as dimethylamine 1 -L, where L is defined as a leaving group such as fluorine, chlorine or bromine, to give a compound of formula V.

[0095] In a still further aspect, the present invention provides a method for preparing a compound of formula XLIV, comprising the steps of: 1 and B 1 is defined with respect to Equation 1); [ka] a34) a compound of formula XLIII (wherein X 11~13 is a protecting group such as acetate) in an organic solvent such as methanol, optionally in the presence of water, in the presence of a base such as triethylamine, sodium hydroxide or sodium methoxide, followed by neutralization using an acid such as HCl to provide a compound of formula XLIV.

[0096] In a still further aspect, the present invention provides a compound of formula XLV, wherein A 1 and B 1 is defined with respect to Formula 1) or a pharmaceutically acceptable salt or solvate thereof, comprising the step a35; [ka] a35) Reaction of a compound of formula XLIV with a reagent such as benzaldehyde dimethyl acetal in the presence of an acid such as D(+)-10-camphorsulfonic acid or p-toluenesulfonic acid in an inert solvent such as DMF or toluene, optionally at elevated temperature and optionally under reduced pressure, and evaporating the methanol to give a compound of formula XLV, wherein X 14 and X 15 together to form a benzylidene).

[0097] In a still further aspect, the present invention provides a compound of formula XLVII, wherein A 1 is defined for compounds of formula 1, and B 3 is the compound of formula 1 in sections b) and d) B 1 Selected from X 17 -CONR 6 R 7 or -CONR 12 R 13 (In the formula, R 6 , R 7 , R 12 and R 13 is defined for compounds of formula 1), methyl, heterocycle, -CN, ethynyl, spiroheterocycle, CONH2, COOH, -SCH3, -COOCH3), comprising step a36; [ka] a36) a compound of formula XLVI, wherein X 16 is defined as -COOH) in an inert solvent such as DMF, optionally in the presence of an organic base such as DIPEA, in the presence of an amide coupling reagent such as HATU, by reaction with HNR 6 R 7 or HNR 12 R 13 to give compounds of formula XLVII, 17 -CONR 6 R 7 or CONR 12 R 13 optionally obtaining a compound of formula XLVI, wherein X16 is a halide such as I, Br, and Cl) with a heterocyclic borinane such as 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane in the presence of Pd(PPh4)3, K2CO3 in an inert solvent such as dioxane, optionally at elevated temperature and optionally under an inert atmosphere, to give a compound of formula XLVII, where X 17 is defined as methyl); optionally obtaining a compound of formula XLVI, 16 is a halide such as I, Br, and Cl) with a heterocyclic dioxaborolane such as 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate using an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and a base such as K2CO3 in an inert solvent such as 1,4-dioxane / water to give a compound of formula XLVII, where X 17 is defined as a heterocycle), optionally heated to 100° C. in a microwave reactor for 1 hour; optionally a compound of formula XLVI, 16 is a halide such as I, Br, and Cl) with a heterocyclic boronic acid such as 3-pyridylboronic acid in an inert solvent such as DMF using an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and a base such as K2CO3 at room temperature to give a compound of formula XLVII, where X 17 is defined as a heterocycle); optionally obtaining a compound of formula XLVI, 16is a halide such as I, Br and Cl) with a heterocyclic stannane such as tributyl(2-pyridyl)stannane, tributyl(oxazol-2-yl)stannane, tributyl(thiazol-2-yl)stannane, using a metalloorganic reagent such as bis(triphenylphosphine)palladium(II) chloride or palladium tetrakis, optionally with CsF, in an inert solvent such as DMF at room temperature or elevated temperature to give a compound of formula XLVII, 17 is defined as a heterocycle); optionally obtaining a compound of formula XLVI, 16 is a halide such as I, Br, and Cl) with a metal cyano reagent such as Zn(CN)2 in an inert solvent such as DMF using a metal organic reagent such as Pd2 (dibenzylideneacetone) and Zn at elevated temperature to give a compound of formula XLVII, where X 17 is defined as —CN); optionally obtaining a compound of formula XLVI (wherein X 16 is a halide such as I, Br and Cl) with ethynyl or TMS-ethynyl in the presence of an organic base in an inert solvent such as DMF, optionally at elevated temperature, in the presence of a metallo-organic reagent such as bis(triphenylphosphine)palladium(II) chloride and CuI to give compounds of formula XLVII, 17 is defined as ethynyl); optionally obtaining a compound of formula XLVI, 16 is a halide such as I, Br, and Cl) with a heterocycle or spiroheterocycle such as a spiroheterocycle such as N-(2-oxa)-6-azaspiro[3.3]heptanyl using an organic base such as DIPEA in an inert solvent such as DMF at elevated temperature such as 130° C. in a microwave reactor to give a compound of formula XLVII, 17 is defined as a heterocycle or a spirocycle; optionally obtaining a compound of formula XLVI, 16 is a cyano group) with a base such as sodium hydroxide in a solvent such as ethanol and water at elevated temperature to give a compound of formula XLVII, where X 17 is —COOH); optionally, a compound of formula XLVI (wherein X16 Ha-COOX 22 and X 22 is defined as aryl or linear or branched C1-C5 alkyl optionally substituted with aryl) with a base such as lithium hydroxide or sodium hydroxide in water, optionally mixed with another organic solvent such as ethanol or acetonitrile, at elevated temperature to produce a compound of formula XLVII, where X 17 is —COOH); optionally to obtain a compound of formula XLVI, 16 is a halide such as I, Br, and Cl) with an alkylthiol nucleophile such as sodium thiomethoxide in a solvent such as DMF to give a compound of formula XLVII, where X 17 is —SCH3); optionally obtaining a compound of formula XLVI, wherein X 16 is COOH) with an alkyl halide such as methyl iodide in the presence of a base such as CsCO3 in a solvent such as DMF to give a compound of formula XLVII, 17 is -COOCH3).

[0098] In a still further aspect, the present invention provides a compound of formula XLIX, wherein B 4 is B in sections b) and d) of Equation 1 1 Selected from X 17 -CONR 6 R 7 or -CONR 12 R 13 (In the formula, R 6 , R 7 , R 12 and R 13 is defined as for formula I), methyl, heterocycle, -CN, ethynyl, spiroheterocycle, CONH2, COOH, -SCH3, -COOCH3), comprising step a37; [ka] a37) a compound of formula XLVIII, 18is defined as -COOH) in an inert solvent such as DMF, optionally in the presence of an organic base such as DIPEA, in the presence of an amide coupling reagent such as HATU, by reaction with HNR 6 R 7 or HNR 12 R 13 to produce a compound of formula XLIX, 19 -CONR 6 R 7 or CONR 12 R 13 optionally obtaining a compound of formula XLVIII (wherein X 18 is a halide such as I, Br, and Cl) with a heterocyclic borinane such as 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane in the presence of Pd(PPh4)3, K2CO3 in an inert solvent such as dioxane, optionally at elevated temperature and optionally under an inert atmosphere, to give a compound of formula XLIX, where X 19 is defined as methyl); optionally obtaining a compound of formula XLVIII (wherein X 18 is a halide such as I, Br, and Cl) with a heterocyclic dioxaborolane such as 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate using an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and a base such as KCO in an inert solvent such as 1,4-dioxane / water to give a compound of formula XLIX, where X 19 is defined as a heterocycle), optionally heated to 100° C. in a microwave reactor for 1 hour; optionally a compound of formula XLVIII (wherein X 18is a halide such as I, Br, and Cl) with a heterocyclic boronic acid such as 3-pyridylboronic acid in an inert solvent such as DMF using an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and a base such as KCO at room temperature to give a compound of formula XLIX, 19 is defined as a heterocycle); optionally obtaining a compound of formula XLVIII, 18 is a halide such as I, Br and Cl) with a heterocyclic stannane such as tributyl(2-pyridyl)stannane, tributyl(oxazol-2-yl)stannane, tributyl(thiazol-2-yl)stannane, using a metalloorganic reagent such as bis(triphenylphosphine)palladium(II) chloride or palladium tetrakis, optionally with CsF, in an inert solvent such as DMF at room temperature or elevated temperature to give a compound of formula XLIX, 19 is defined as a heterocycle); optionally obtaining a compound of formula XLVIII, 18 is a halide such as I, Br, and Cl) with a metal cyano reagent such as Zn(CN)2 in an inert solvent such as DMF using a metal organic reagent such as Pd2 (dibenzylideneacetone) and Zn at elevated temperature to give a compound of formula XLIX, where X 19 is defined as —CN); optionally obtaining a compound of formula XLVIII (wherein X 18 is a halide such as I, Br and Cl) with ethynyl or TMS-ethynyl in the presence of an organic base in an inert solvent such as DMF, optionally at elevated temperature, in the presence of a metallo-organic reagent such as bis(triphenylphosphine)palladium(II) chloride and CuI to give compounds of formula XLIX, 19 is defined as ethynyl); optionally obtaining a compound of formula XLVIII (wherein X 18is a halide such as I, Br, and Cl) with a heterocycle or spiroheterocycle such as a spiroheterocycle such as N-(2-oxa)-6-azaspiro[3.3]heptanyl using an organic base such as DIPEA in an inert solvent such as DMF at elevated temperature such as 130° C. in a microwave reactor to give a compound of formula XLIX, 19 is defined as a heterocycle or a spirocycle; optionally obtaining a compound of formula XLVIII, 18 is a cyano group) with a base such as sodium hydroxide in a solvent such as ethanol and water at elevated temperature to give a compound of formula XLIX, where X 19 is —COOH); optionally, a compound of formula XLVIII (wherein X is —COOH) can be obtained. 18 Ha-COOX 22 and X 22 is defined as aryl or linear or branched C1-C5 alkyl optionally substituted with aryl) with a base such as lithium hydroxide or sodium hydroxide in water, optionally mixed with another organic solvent such as ethanol or acetonitrile, at elevated temperature to produce a compound of formula XLIX, where X 19 is —COOH); optionally to obtain a compound of formula XLVIII (wherein X 18 is a halide such as I, Br, and Cl) with an alkylthiol nucleophile such as sodium thiomethoxide in a solvent such as DMF to give a compound of formula XLIX, 19 is —SCH3); optionally obtaining a compound of formula XLVIII (wherein X 18 is COOH) with an alkyl halide such as methyl iodide in the presence of a base such as CsCO3 in a solvent such as DMF to give a compound of formula XLIX, 19 is -COOCH3).

[0099] In a still further aspect, the present invention provides a compound of formula XLXII, wherein B 1 is defined in Equation 1, and X 20 is defined as a protecting group), the method comprising steps a38 to a39; [ka] a38) reacting a compound of formula L with a compound of formula X in the presence of a base such as DIPEA in an inert solvent such as dioxane at elevated temperature 20 -SH compound (wherein X 20 is a protecting group such as a benzyl group) to provide a compound of formula LI; optionally, the compound of formula L is reacted with (2,4-dimethoxyphenyl)methanethiol, optionally in the presence of a ligand such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, in the presence of a metallo-organic ligand such as bis(dibenzylideneacetone)palladium, to provide a compound of formula LI. a39) Reacting a compound of formula LI with AlCl3 in a solvent such as toluene to give a compound of formula LII; optionally reacting a compound of formula LI in the presence of TFA and triethylsilane to give a compound of formula LII.

[0100] In yet a further aspect, the present invention provides a compound of formula LIV, wherein B 5 X 22 is B in b) and d) of Equation 1 1 (defined as) [ka] a40) a compound of formula LIII (wherein X 21 is defined as cyano) with 2,2-dimethoxyethanamine in the presence of a strong base such as sodium methoxide, followed by the addition of an acid such as acetic acid to give a compound of formula LIV, where X 22 is imidazole). [ka] optionally a compound of formula LIII, wherein X 21is defined as SH) with 3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole in a solvent such as DCM to give a compound of formula LIV, where X 22 is CF3).

[0101] In a still further aspect, the present invention provides compound B 1 -Br with 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane in the presence of Pd(PPh4)3, K2CO3 in an inert solvent such as dioxane, optionally at elevated temperature and optionally under an inert atmosphere, to give 1 -CH3 compounds (wherein B 1 relates to a method for preparing a compound as defined in relation to formula 1 in sections b) and d).

[0102] In the above reaction steps a1-a40, whenever diastereoisomeric compounds are prepared, they can be separated by chromatography, such as using HPLC. Additionally, in the above process steps a1-a40, the anomeric sulfur can be replaced by O, SO, or SO under similar reaction conditions to prepare analogs in which S is replaced. DETAILED DESCRIPTION OF THE INVENTION

[0103] The present compounds of formula (1) differ from prior art compounds, particularly in that the pyranose ring is α-D-galactopyranose. It is important to emphasize that the α-anomer and β-anomer are very different isomers, and it would never be obvious to one skilled in the art to expect the same or similar activity for both anomers. As a result, the α-anomer and β-anomer do not generally have the same activity, which is common knowledge among those skilled in the art. The compounds of the present invention unexpectedly exhibit very high affinity and specificity for galectin-1, making them novel α-D-galactopyranose compounds considered to be novel, powerful drug candidates. Some of the novel α-D-galactopyranose compounds have affinity for both galectin-1 and galectin-3, and therefore have a broader disease treatment profile than selective galectin-1 inhibitors.

[0104] In a broad aspect, the present invention provides a D-galactopyranose compound of formula (1): [ka] (In the formula, The pyranose ring is α-D-galactopyranose, and A1, R1, X and B1 are as defined above. Regarding.

[0105] When A1 is of formula 2, preferably [ka] [ka] or [ka] is selected from.

[0106] A1 is [ka] and when X is S, R1 is OC 1~4 OC substituted with at least one group from the group consisting of alkyl, such as O-methyl, O-ethyl or O-isopropyl, phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1~4 alkyl, and B1 is selected from Cl, Br, CN; C2-alkynyl; methyl; CF3; pyridine; pyrimidine; oxazole; and pyridinyl optionally substituted with a group selected from thiazole; and halogen, CN, -CONR 6 R 7 (In the formula, R 6 and R 7 is H, C 1~3 alkyl, cyclopropyl, and isopropyl), and C optionally substituted with F 1~3 Preferably, R is selected from phenyl optionally substituted with a group selected from alkyl. 1 is selected from methoxy, methoxy substituted with one phenyl, and methoxy substituted with one phenyl substituted with one to three groups selected from OH and halogens, for example F and Cl. Preferably, B1 is selected from Cl, Br, C2-alkynyl, pyridinyl substituted with groups selected from CN; and one to three halogens selected from, for example, F, Br and / or Cl; CN and CONR 6 R 7 (In the formula, R 6 and R 7 is H and C 1~3 phenyl substituted with a group selected from (independently selected from alkyl).

[0107] A1 is [ka] and when X is S, R1 is H, OH, OC 1~4OC substituted with at least one group from the group consisting of alkyl, such as O-methyl, O-ethyl or O-isopropyl, phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1~4 alkyl, and B1 is selected from Cl, Br, CN, C2-alkynyl, methyl, CF3, -CONR 12 R 13 (In the formula, R 12 and R 13 is H, C 1~3 independently selected from alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 together with the nitrogen form a heterocycloalkyl), pyridinyl optionally substituted with a group selected from pyridine, pyrimidine, oxazole and thiazole, or Br, Cl, CN and CONR 6 R 7 (In the formula, R 6 and R 7 is H and C 1~3 Preferably, R1 is selected from H, OH, methoxy or ethoxy, e.g., methoxy. Preferably, B1 is selected from Cl, C2-alkynyl, methyl, Br, CO-azididinyl, CON(CH3)2, CONHCH3, CONHCH2CH3, pyridinyl or pyridinyl substituted with one to three substituents selected from CN. Preferably, B1 is selected from phenyl substituted with one to three substituents selected from Br, Cl, CN and CONHCH3.

[0108] A1 is [ka] and when X is S, R1 is OC 1~4OC substituted with at least one group from the group consisting of alkyl, such as O-methyl, O-ethyl or O-isopropyl, phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1~4 alkyl, and B1 is selected from Cl, Br, C2-alkynyl, CN; methyl; CF3; pyridine; pyrimidine; oxazole; and pyridinyl optionally substituted with a group selected from thiazole; and C1 optionally substituted with halogen and optionally F. 1~3 Preferably, R1 is selected from phenyl optionally substituted with a group selected from alkyl. Preferably, R1 is O-methyl. Preferably, B1 is pyridinyl substituted with a group selected from Cl, Br, CN; methyl; and pyridine. Preferably, B1 is phenyl substituted with a group selected from halogen, such as F or Br.

[0109] When A1 is of formula 3, preferably [ka] [ka] or [ka] is selected from.

[0110] A1 is [ka] and when X is S, R1 is H, OH, OC 1~4 alkyl, such as O-methyl, O-ethyl or O-isopropyl, optionally substituted with one or more halogens; 1~4 OC substituted with at least one group selected from the group consisting of alkyl, phenyl, and phenyl substituted with one or more groups selected from OH and halogen;1~4 alkyl, and B1 is selected from Cl; Br; C2-alkynyl; CN; methyl; CF3; pyridine; imidazole; pyrimidine; oxazole; tetrahydrobipyridine; spiroheterocycle; and pyridinyl optionally substituted with a group selected from thiazole; and C1 optionally substituted with halogen and optionally F. 1~3 Preferably, R1 is selected from phenyl optionally substituted with a group selected from alkyl. Preferably, R1 is selected from H, OH, methoxy, ethoxy, OCH2CF3, or methoxy substituted with 1 to 3 groups selected from the group consisting of phenyl and phenyl substituted with 1 to 3 groups selected from OH and halogen. Preferably, B1 is selected from pyridinyl, Cl, Br, pyridinyl substituted with 1 to 3 groups selected from C2-alkynyl; CN; methyl; CF3; N-(2-oxa)-6-azaspiro[3.3]heptanyl; pyridine; imidazole; pyrimidine; oxazole; tetrahydrobipyridine; and thiazole. Preferably, B1 is selected from F, Cl, Br, CN, and C2-alkynyl optionally substituted with F. 1~3 phenyl substituted with 1 to 3 groups selected from alkyl.

[0111] A1 is [ka] and when X is S, R1 is H, OH, OC 1~4 Alkyl, e.g., O-methyl, O-ethyl or O-isopropyl, OC substituted with halogen 1~4 OC substituted with at least one group selected from the group consisting of alkyl, phenyl, and phenyl substituted with one or more groups selected from OH and halogen; 1~4 alkyl, and B1 is selected from Cl; Br; CN; C2-alkynyl; methyl; CF3; pyridine; imidazole; pyrimidine; oxazole; tetrahydrobipyridine; and pyridinyl optionally substituted with a group selected from thiazole; and halogen, CN and C optionally substituted with F. 1~3Preferably, R1 is selected from phenyl optionally substituted with a group selected from alkyl. Preferably, R1 is selected from H, OH, methoxy, ethoxy, isopropyloxy, or OCH2CF3. Preferably, B1 is selected from phenyl substituted with 1 to 3 groups selected from CN, Cl, Br, or F. Preferably, B1 is selected from pyridine substituted with 1 to 3 groups selected from CN, Cl, and imidazole.

[0112] A1 is [ka] and when X is S, R1 is OC 1~4 OC substituted with at least one group from the group consisting of alkyl, such as O-methyl, O-ethyl or O-isopropyl, or phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1~4 Preferably, R1 is selected from alkyl, and B1 is selected from pyridinyl optionally substituted with a group selected from Cl, Br, CN; C2-alkynyl; methyl; CF3; pyridine; pyrimidine; oxazole; tetrahydrobipyridine; and thiazole. Preferably, R1 is selected from methoxy, ethoxy, or isopropyloxy, such as methoxy. Preferably, B1 is selected from pyridinyl optionally substituted with 1 to 3 groups selected from Cl, Br, CN.

[0113] A1 is formula 2 and R 2 is a halogen and R 3 C 1~6 When X is S, R1 is selected from the group consisting of alkyl and halogen, and when X is S, R1 is selected from the group consisting of OC 1~4 In one embodiment, A is of formula 2, R 2 is Cl and R 3 is selected from the group consisting of methyl and halogen.

[0114] In a further embodiment, the compound of formula (1) is 3,5-dichloro-4-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 2-O-benzyl-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-bromo-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyrimidin-5-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(thiazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-4-(trifluoromethyl)phenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3-bromo-2-trifluoromethylpyridin-5-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-deoxy-3-[4-(4-methyltriazol-2-yl)-1H-1,2,3-thiazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptanyl}pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside, 3-cyano-2-(trifluoromethyl)pyridin-5-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-azetidinylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3-chloro-5-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4,5-dichlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-(N-methylcarbonyl)phenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 2,5-dichlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-chlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-fluorophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-ethyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-2-O-(2,2,2-trifluoroethyl)-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-(N,N-dimethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-ethynyl-2-(N,N-dimethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynyl-2-(N-azetidinylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-ethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 1,3-benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 1,3-Benzothiazol-6-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 1,3-Benzothiazol-6-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyano-1,3-benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, Thiazolo[4,5-b]pyridin-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-Methylsulfanylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, and 5-(Trifluoromethylsulfanyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside is selected from one of the following.

[0115] Those skilled in the art will understand that it may be necessary to adjust or change the order of the steps in Methods a1-a40, and that such changes in order are encompassed within the process aspects described above in the reaction schemes and accompanying description of the process steps.

[0116] Additionally, those skilled in the art will recognize that in the methods described above and below, it may be necessary to protect the functional groups of intermediate compounds with protecting groups.

[0117] Functional groups that it is desirable to protect include hydroxy, amino, and carboxylic acid. Suitable protecting groups for hydroxy include optionally substituted and / or unsaturated alkyl groups (e.g., methyl, allyl, benzyl, or tert-butyl), trialkylsilyl or diarylalkylsilyl groups (e.g., t-butyldimethylsilyl, t-butyldiphenylsilyl, or trimethylsilyl), AcO (acetoxy), TBS (t-butyldimethylsilyl), TMS (trimethylsilyl), PMB (p-methoxybenzyl), and tetrahydropyranyl. Suitable protecting groups for carboxylic acid include (C 1~6 )-alkyl or benzyl esters. Suitable protecting groups for amino include t-butyloxycarbonyl, benzyloxycarbonyl, 2-(trimethylsilyl)-ethoxy-methyl or 2-trimethylsilylethoxycarbonyl (Teoc). Suitable protecting groups for S include SC(=N)NH2, TIPS.

[0118] Protection and deprotection of functional groups can be carried out before or after the reaction in the above-mentioned methods.

[0119] Additionally, one of ordinary skill in the art will recognize that the individual process steps described above can be performed in a different order, and / or individual reactions can be performed at different stages in the overall pathway (i.e., substituents can be added and / or chemical transformations can be performed on different intermediates than those described above in connection with a particular reaction) to obtain the compounds of the present invention in an alternative, and in some cases more convenient, manner, which can negate or require the need for protecting groups.

[0120] In yet a further embodiment, compound (1) is in free form. As used herein, "in free form" refers to the compound of formula (1) in acid or base form, or as a neutral compound, depending on the substituents. The free form does not further have an acid or base salt. In one embodiment, the free form is an anhydrate. In another embodiment, the free form is a solvate (e.g., a hydrate).

[0121] In a further embodiment, the compound of formula (1) is in a crystalline form. Those skilled in the art can conduct tests to find polymorphs, and such polymorphs are intended to be encompassed by the term "crystalline form" as used herein.

[0122] When the compounds and pharmaceutical compositions disclosed herein are used for the above treatments, a therapeutically effective amount of at least one compound is administered to a mammal in need of said treatment.

[0123] As used herein, "C 1~x The term "alkyl" refers to an alkyl group containing 1 to x carbon atoms, e.g., C 1~5 or C 1~6 , for example methyl, ethyl, propyl, butyl, pentyl or hexyl.

[0124] As used herein, "branch C" 3~6 The term "alkyl" means a branched alkyl group containing 3 to 6 carbon atoms, for example, isopropyl, isobutyl, tert-butyl, isopentyl, 3-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl.

[0125] As used herein, "C 3~7 The term "cycloalkyl" means a cyclic alkyl group containing from 3 to 7 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and 1-methylcyclopropyl.

[0126] As used herein, "C 5~7 The term "cycloalkyl" means a cyclic alkyl group containing 5 to 7 carbon atoms, for example, cyclopentyl, cyclohexyl, or cycloheptyl.

[0127] The term "C2 alkynyl" as used herein means -CCH, where two carbons are joined by a triple bond.

[0128] The term "oxo" as used herein means an oxygen atom having a double bond, also depicted as =O.

[0129] As used herein, the term "CN" means nitrile.

[0130] As used herein, the term "5- or 6-membered heteroaromatic ring" refers to a 5- or 6-membered heteroaromatic ring. A 5-membered heteroaromatic ring contains 5 ring atoms, 1 to 4 of which are heteroatoms selected from N, O, and S. A 6-membered heteroaromatic ring contains 6 ring atoms, 1 to 5 of which are heteroatoms selected from N, O, and S. Examples include thiophene, furan, pyran, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, and pyridazine. When such heteroaromatic rings are substituents, they are referred to as thiophenyl, furanyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, pyridinyl, pyrazinyl, pyrimidinyl, and pyridazinyl. Also included are oxazoyl, thiazoyl, thiadiazolyl, oxadiazoyl, and pyridonyl.

[0131] As used herein, the term "heterocycle, e.g., heteroaryl or heterocycloalkyl" refers to a heterocycle consisting of one or more 3- to 7-membered ring systems containing one or more heteroatoms, which may optionally be aromatic. As used herein, the term "heteroaryl" refers to a monocyclic or bicyclic aromatic ring system containing one or more heteroatoms, 1 to 10, e.g., 1 to 6, selected from O, S, and N, including, but not limited to, benzothiazolyl, oxazolyl, oxadiazolyl, thiophenyl, thiadiazolyl, thiazolyl, thiazolopyridinyl, pyridyl, pyrimidinyl, pyridonyl, pyrimidonyl, quinolinyl, azaquionolyl, isoquinolinyl, azaisoquinolyl, quinazolinyl, azaquinazolinyl, benzozazoyl, azabenzoxazoyl, benzothiazoyl, or azabenzothiazoyl. The term "heterocycloalkyl" as used herein means a monocyclic or bicyclic 3-7 membered aliphatic heterocycle containing one or more heteroatoms, such as 1 to 7, e.g., 1 to 5, selected from O, S, and N, including, but not limited to, azetidinyl, piperidinyl, tetrahydropyranyl, tetrahydrothipyranyl, or piperidonyl.

[0132] As used herein, the terms "treatment" and "treating" refer to the management and care of a patient for the purpose of combating a condition, such as a disease or disorder. This term includes the full range of treatments for a given condition from which a patient is suffering, such as the administration of active compounds to alleviate symptoms or complications, delay the progression of a disease, disorder, or condition, alleviate or relieve symptoms and complications, and / or cure or eliminate a disease, disorder, or condition, as well as to prevent a condition, where prevention is to be understood as the management and care of a patient for the purpose of combating a disease, condition, or disorder, and includes the administration of active compounds to prevent the onset of symptoms or complications. Treatment can be carried out either acutely or chronically. The patient to be treated is preferably a mammal, particularly a human, but can also include animals such as dogs, cats, cows, sheep, and pigs.

[0133] As used herein, the term "therapeutically effective amount" of the compound of formula (1) of the present invention means an amount sufficient to cure, alleviate, or partially prevent the clinical symptoms of a given disease and its complications. An amount sufficient to achieve this is defined as a "therapeutically effective amount." The effective amount for each purpose depends on the severity of the disease or injury and the weight and general condition of the subject. It is understood that determining the appropriate dosage can be achieved using routine experimentation, by constructing a matrix of values ​​and testing different points in the matrix, all of which is within the ordinary skill of a trained physician or veterinarian.

[0134] In a still further aspect, the present invention relates to a pharmaceutical composition comprising a compound of formula (1) and optionally a pharmaceutically acceptable excipient, such as a carrier or diluent.

[0135] As used herein, "pharmaceutically acceptable excipients" is intended to include, but is not limited to, carriers, excipients, diluents, adjuvants, colorants, fragrances, preservatives, and the like that one skilled in the art would consider using when formulating the compounds of the present invention to produce pharmaceutical compositions.

[0136] The adjuvants, diluents, excipients and / or carriers that can be used in the compositions of the present invention must be pharmaceutically acceptable in the sense that they are compatible with the compound of formula (1) and other ingredients of the pharmaceutical composition and are not harmful to the recipient. Preferably, the compositions should not contain substances that can cause adverse reactions, such as allergic reactions. The adjuvants, diluents, excipients and carriers that can be used in the pharmaceutical compositions of the present invention are well known to those skilled in the art.

[0137] As described above, the compositions disclosed herein, particularly pharmaceutical compositions, can further comprise at least one pharmaceutically acceptable adjuvant, diluent, excipient, and / or carrier in addition to the compounds disclosed herein. In some embodiments, the pharmaceutical composition comprises 1 to 99% by weight of the at least one pharmaceutically acceptable adjuvant, diluent, excipient, and / or carrier and 1 to 99% by weight of the compounds disclosed herein. The combined amount of the active ingredient and the pharmaceutically acceptable adjuvant, diluent, excipient, and / or carrier cannot comprise more than 100% by weight of the composition, particularly the pharmaceutical composition.

[0138] In some embodiments, only one compound disclosed herein is used for the above purposes.

[0139] In some embodiments, two or more of the compounds disclosed herein are used in combination for the above purposes.

[0140] The compositions, particularly pharmaceutical compositions, comprising the compounds provided herein can be adapted for oral, intravenous, topical, intraperitoneal, nasal, buccal, sublingual or subcutaneous administration, or for administration via the respiratory tract, for example, in the form of aerosol or air-suspended fine powder.Therefore, the pharmaceutical compositions can be in the form of, for example, tablets, capsules, powders, nanoparticles, crystals, amorphous substances, solutions, transdermal patches or suppositories.

[0141] Further embodiments of this method are described in the Experimental Section herein, with each individual method and each starting material constituting an embodiment that may form part of an embodiment.

[0142] The above embodiments should be considered to refer to any one of the aspects described herein (e.g., "method of treating," "pharmaceutical composition," "compound for use as a pharmaceutical," or "compound for use in a method," etc.) as well as any one of the embodiments described herein, unless it is specified that the embodiment relates to one or more particular aspects of the invention.

[0143] All references, including publications, patent applications, and patents, cited in this specification are herein incorporated by reference to the same extent as if each individual reference was individually and specifically indicated to be incorporated by reference and was set forth in its entirety herein.

[0144] All headings and sub-headings are used herein for convenience only and should not be construed as limiting the invention in any way.

[0145] Any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

[0146] As used in the context of describing the present invention, the terms "a," "an," and "the" and similar referents should be construed to encompass both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0147] The recitation of ranges of values ​​herein, unless otherwise indicated herein, is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, and each separate value is incorporated herein as if it were individually recited herein. Unless otherwise specified, all exact values ​​provided herein represent corresponding approximations (e.g., all exact exemplary values ​​provided with respect to a particular factor or measurement can also be considered to provide the corresponding approximate measurement, modified by "about," as appropriate).

[0148] All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context.

[0149] Any and all examples provided herein, or the use of exemplary language (e.g., "etc.") are intended merely to better illustrate the invention and do not limit the scope of the invention unless specifically indicated. No language in the specification should be construed as indicating any element essential to the practice of the invention unless explicitly stated.

[0150] The citation and incorporation of patent documents herein is for convenience only and does not reflect any view as to the validity, patentability and / or enforceability of such patent documents.

[0151] As used herein, the term "and / or" is intended to refer to both alternatives and each of the alternatives individually. For example, the phrase "xxx and / or yyy" means "xxx and yyy"; "xxx"; or "yyy", with all three alternatives being according to individual embodiments.

[0152] Any description herein of any aspect or embodiment of the invention using terms such as "comprising," "having," "including," or "containing," in reference to one or more elements, is intended to provide support for similar aspects or embodiments of the invention that "consist," "consist essentially of," or "substantially comprise" one or more particular elements, unless otherwise stated or clearly contradicted by context (e.g., a composition described herein as comprising a particular element should be understood to also describe a composition consisting of that element, unless otherwise stated or clearly contradicted by context). The present invention includes all modifications and equivalents of the subject matter recited in the aspects or claims presented herein to the maximum extent permitted by applicable law.

[0153] The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of protection. The features disclosed in the foregoing description and in the following examples may, both individually and in any combination thereof, be material for realizing the invention in diverse forms thereof.

[0154] Experimental procedure (evaluation of Kd value) The affinity of Examples 1-103 for galectins was evaluated by Sorme, P., Kahl-Knutsson, B., Huflejt, M., Nilsson, U. J., and Leffler, H. (2004) Fluorescence polarization as an analytical tool to evaluate galectin-ligand interactions. Anal. Biochem. 334:36-47 (Sorme et al., 2004) and Monovalent interactions of Galectin-1 by Salomonsson, Emma; Larumbe, Amaia; Tejler, Johan; Tullberg, Erik; Rydberg, Hanna; Sundin, Anders; Khabut, Areej; Frejd, Torbjorn; Lobsanov, Yuri D.; Rini, James The galectin-binding domains were determined by fluorescence anisotropy assay using the compounds as inhibitors of the interaction between galectins and fluorescein-tagged glycoprobes as described in M. et al., Biochemistry (2010), 49(44), 9518-9532 (Salomonsson et al., 2010). [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7]

Table 1-8

Table 1-9

Table 1-10

Table 1-11

Table 1-12

Table 1-13

Table 1-14

Table 1-15

Table 1-16

Table 1-17

Table 1-18

Table 1-19

Table 1-20

Table 1-21

[0155] R in Equation 1 1 For some compounds of the invention where the hydroxyl group is alkylated, e.g., —OCH3, high uptake and no efflux are observed in the CACO-2 model of human intestinal uptake, predicting a high likelihood of high human oral bioavailability. In this model (see Artursson, P.; Ungell, A.-L.; Lofroth, J.-E. Selective Paracellular Permeability in Two Models of Intestinal Absorption: Cultured Monolayers of Human Intestinal Epithelial Cells and Rat Intestinal Segments. Pharm. Res. 1993, 10(8), 1123-1129), Example 1 exhibits an apical-to-basolateral (A>B) Papp of 20*10^-6 cm / sec and a basolateral-to-apical (B>A) Papp of 28*10^-6 cm / sec, implying very high uptake and virtually no efflux.

[0156] Synthesis of Examples and Intermediates General Experiments: Nuclear magnetic resonance (NMR) spectra were recorded at 25°C on a 400 MHz Bruker AVANCE III 500 instrument or a 400 MHz Varian instrument.

[0157] Chemical shifts are reported in ppm (d) using residual solvent as the internal standard. Peak multiplicities are denoted as follows: s, singlet; d, doublet; dd, doublet of doublet; t, triplet; dt, triplet of triplet; q, quartet; m, multiplet; br s, broad singlet. For anomeric mixtures, the shifts of the individual anomers are reported separately, and the α / β ratios were calculated based on the integrals of the anomeric peaks.

[0158] LC-MS data were obtained on an Agilent 1200 HPLC coupled to an Agilent MSD mass spectrometer operating in ES(+) ionization mode. Columns: XBridge C18 (4.6 × 50 mm, 3.5 μm) or SunFire C18 (4.6 × 50 mm, 3.5 μm). Solvent A: water + 0.1% TFA and Solvent B: acetonitrile + 0.1% TFA or Solvent A: water (10 mM ammonium bicarbonate) and Solvent B: acetonitrile. Wavelength: 254 nM. Alternatively, LC-MS data were obtained on an Agilent 1100 HPLC coupled to an Agilent MSD mass spectrometer operating in ES(+) ionization mode. Columns: Waters symmetry 2.1 × 30 mm C18 or Chromolith RP-18 2 × 50 mm. Solvent A: water + 0.1% TFA and Solvent B: acetonitrile + 0.1% TFA. Wavelength: 254nm.

[0159] Preparative HPLC was performed on a Gilson 281. Flow rate: 20 mL / min. Column: X-Select 10 μm 19 x 250 mm column. Wavelength: 254 nm or 214 nm. Solvent A: water (10 mM ammonium bicarbonate) and solvent B: acetonitrile. Alternatively, preparative HPLC was performed on a Gilson 215. Flow rate: 25 mL / min. Column: XBrige prep C18 10 μm OBD (19 x 250 mm) column. Wavelength: 254 nm. Solvent A: water (10 mM ammonium bicarbonate) and solvent B: acetonitrile. Alternatively, preparative HPLC was obtained on a Gilson system. Flow rate: 15 mL / min. Column: kromasil 100-5-C18 column. Wavelength: 220 nm. Solvent A: water + 0.1% TFA and solvent B: acetonitrile + 0.1% TFA.

[0160] The following abbreviations are used: aq: water-based Calcd: Calculated value MeCN: acetonitrile CuI: Copper iodide DCM: dichloromethane DIPEA: Diisopropylethylamine DMF: N,N-dimethylformamide ESI-MS: Electrospray ionization mass spectrometry EtOAc or EA: Ethyl acetate Et3N: Triethylamine GC: Gas chromatography h: time HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate HPLC: High-performance liquid chromatography LC: liquid chromatography MeCN: acetonitrile mL: milliliter MeOH: Methanol MeOD: deuterated methanol mm: millimeters mM: millimolar concentration MS: Mass spectrometry nm: nanometer NaI: sodium iodide NaOMe: sodium methoxide N2: Nitrogen gas NMR: nuclear magnetic resonance Pd(PPh3)4: Tetrakis(triphenylphosphine)palladium(0) PE: Petroleum ether pH: acidity Prep: preparative rt: room temperature TBAF: Tetrabutylammonium fluoride TFA: Trifluoroacetic acid THF: tetrahydrofuran TMS: trimethylsilyl UV: Ultraviolet light Å: Angstrom

[0161] Synthesis of Examples 1-103 from respective intermediates 1-103.

[0162] Example 1 3,5-Dichloro-4-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 3,5-dichloro-4-fluorophenyl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (76 mg, 0.13 mmol) in DCM (10 mL) was added TFA (0.5 mL, 6.73 mmol) and HO (0.5 mL). The mixture was stirred at rt for 12 h. EtN (2.0 mL) was added dropwise at 0 °C. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (54 mg, 84%). ESI-MS m / z calcd for [C 18 H 17 Cl2FN4O4S2] [M+H] + :507.0;found:507.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.50(s,1H),7.79(d,J=3.2 Hz,1H),7.66(d,J=6.0 Hz,2H),7.54(d,J=3.2,1H),6.08(d,J=5.2 Hz,1H),4.95(dd,J=11.2,2.8 Hz,1H),4.52(dd,J=11.2,5.2 Hz,1H),4.39-4.36(m,1H),4.10(d,J=2.4 Hz,1H),3.62-3.60(m,2H),3.31(s,3H).

[0163] Example 2 5-Bromopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.34 mmol) in TFA (0.5 mL) and DCM (5 mL) was stirred at rt for 2 h. The pH was adjusted to 7-8 by dropwise addition of saturated aqueous NaHCO3. Water (10 mL) and DCM (15 mL) were added, and the phases were separated. The isolated aqueous phase was further extracted with DCM (2 × 10 mL). The combined organic layers were concentrated and purified by preparative HPLC (X-Select 10 μm 19*250 mm, 20 mL / min, MeCN / H2O (10 mmol / L NH4HCO3) = 40-90%) to give the title compound (90 mg, 63%). ESI-MS m / z calculation for [C 17 H 18 BrNOS2] [M+H] + :500.0,found:500.0 1 H NMR(400 MHz,Methanol-d4)δ 8.60(d,J=1.8 Hz,1H),8.51(s,1H),8.48(d,J=2.1 Hz,1H),8.26(t,J=2.0 Hz,1H),7.80(d,J=3.3 Hz,1H),7.55(d,J=3.3 Hz,1H),6.18(d,J=5.3 Hz,1H),4.99(dd,J=11.4,2.9 Hz,1H),4.55(dd,J=11.4,5.3 Hz,1H),4.37(t,J=5.9 Hz,1H),4.11(d,J=1.9 Hz,1H),3.63-3.52(m,2H),3.32(s,3H).

[0164] Example 3 5-Bromo-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-deoxy-2-O-methyl-3-[4-(thiazol-2-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (57.0 mg, 0.094 mmol) in MeOH (3.0 mL), EtN (2.0 mL), and water (1.0 mL) was stirred at rt for 4 h. The mixture was concentrated and purified by preparative HPLC (X-Select 10 μm 19*250 mm, 20 mL / min, MeCN / HO (10 mmol / L NHHCO) = 40-90%) to give the title compound (22.0 mg, 45%). ESI-MS m / z calculation for [C 18 H 17 BrN6O4S2] [M+H] + :525.0,found:525.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.73(d,J=2.0 Hz,1H),8.65(d,J=2.0 Hz,1H),8.64(s,1H),7.91(d,J=3.6 Hz,1H),7.66(d,J=3.2 Hz,1H),6.53(d,J=5.2 Hz,1H),5.16(dd,J=11.2,2.8 Hz,1H),4.74(dd,J=11.2,5.2 Hz,1H),4.43(t,J=6.0 Hz,1H),4.24(d,J=2.4 Hz,1H),3.70(d,J=6.0 Hz,2H),3.40(s,3H).

[0165] Example 4 5-Chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (90.0 mg, 0.16 mmol) in DCM / TFA (10.0 mL, 19:1) was stirred at rt for 1 h. The pH of the mixture was adjusted to approximately 8 with EtN, followed by evaporation of the solvent. The residue was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3) = 0-20%, X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (40.5 mg, 53%). ESI-MS m / z calculation for [C 18 H 17 ClN6O4S2] [M+H] + :481.0,found:481.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.56-8.47(m,2H),8.38(d,J=2.1 Hz,1H),7.80(d,J=3.3 Hz,1H),7.55(d,J=3.3 Hz,1H),6.42(d,J=5.3 Hz,1H),5.04(dd,J=11.3,2.8 Hz,1H),4.62(dd,J=11.3,5.3 Hz,1H),4.31(t,J=6.0 Hz,1H),4.13(d,J=2.4 Hz,1H),3.66-3.52(m,2H),3.37(s,3H).

[0166] Example 5 5-Chloro-2-cyanopyridin-3-yl 2-O-benzyl-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanopyridin-3-yl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (68 mg, 0.11 mmol) in DCM / TFA (5 mL, 4:1) was stirred at rt for 3 h. The mixture was neutralized with EtN and evaporated. The residue was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (23.3 mg, 40%). ESI-MS m / z calcd for [C 24 H 21 ClN6O4S2] [M+H] + :557.1;found:557.0. 1 H NMR(400 MHz,DMSO-d6)δ 8.75(d,J=2.0 Hz,1H),8.69(s,1H),8.56(d,J=2.0 Hz,1H),7.95(d,J=3.2 Hz,1H),7.80(d,J=3.2 Hz,1H),7.26-7.16(m,3H),7.16-7.07(m,2H),6.69(d,J=5.2 Hz,1H),5.67(d,J=6.0 Hz,1H),5.01(ddd,J=16.8,11.2,4.0 Hz,2H),4.86-4.72(m,2H),4.54(d,J=11.2 Hz,1H),4.31-4.20(m,1H),4.15-4.06(m,1H),3.59-3.39(m,2H).

[0167] Example 6 5-Chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-deoxy-2-O-(3,5-difluoro-4-(4-methoxybenzyloxy)benzyl)-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (120 mg, 0.14 mmol) in DCM (5 mL) was added TFA (502 mg, 4.4 mmol) and HO (0.5 mL), and the mixture was stirred at rt for 12 h. EtN (1.0 mL) was added dropwise at 0 °C. The mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (30 mg, 34%). ESI-MS m / z calcd for [C 24 H 19 ClF2N6O5S2] [M+H] + :609.1;found:609.1. 1 H NMR(400 MHz,Methanol-d4)δ 8.51(d,J=2.0 Hz,1H),8.39-8.37(m,1H),8.34(d,J=2.0 Hz,1H),7.80(d,J=3.2 Hz,1H),7.54(d,J=3.6 Hz,1H),6.59-6.50(m,2H),6.30(d,J=5.6 Hz,1H),5.08(dd,J=11.2,2.8 Hz,1H),4.73(dd,J=11.2,5.6 Hz,1H),4.56(d,J=11.6 Hz,1H),4.35-4.29(m,2H),4.12(d,J=2.8 Hz,1H),3.60-3.58(m,2H).

[0168] Example 7 3,5-Dichloro-4-fluorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 3,5-dichloro-4-fluorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (35.0 mg, 0.057 mmol) in DCM / TFA (3 mL, 19:1) was stirred at rt for 3 h. EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3) = 40-80%, X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (20.9 mg, 70%). ESI-MS m / z calculation for [C 18 H 17 Cl2FN4O5S2] [M+H] + :523.0;found:523.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.35(s,1H),7.74(d,J=6.3 Hz,2H),6.70(s,1H),6.16(d,J=5.3 Hz,1H),4.99(dd,J=11.4,2.8 Hz,1H),4.53(dd,J=11.4,5.3 Hz,1H),4.45(t,J=6.0 Hz,1H),4.16(d,J=2.4 Hz,1H),3.75-3.61(m,2H),3.38(s,3H).

[0169] Example 8 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-isopropyl-1-thio-α-D-galactopyranoside (80 mg, 0.16 mmol) and 4-(2-trimethylsilylethynyl)thiazol-2-ol (63.6 mg, 0.32 mmol) in DMF (2 mL) was added DIPEA (0.138 mL, 0.81 mmol), followed by CsF (49 mg, 0.32 mmol) and CuI (9.21 mg, 0.048 mmol), and the mixture was stirred at rt for 4 h. The mixture was diluted with water (5 mL) and extracted with DCM. The organic phase was washed with water (6 × 5 mL) and concentrated. The residue was stirred in DCMTFA (5.25 mL, 20:1) at rt for 2 h. The pH of the mixture was adjusted to pH = 8 using Et3N. The mixture was concentrated and purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3) = 0-50%, X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (10.1 mg, 12%). ESI-MS m / z calculation for [C 20 H 22 Cl2N4O5S2] [M+H] + :533.0,found:533.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.30(s,1H),7.68(d,J=1.9 Hz,1H),7.41(dt,J=16.1,5.2 Hz,2H),6.61(s,1H),6.00(d,J=5.3 Hz,1H),4.91(dd,J=11.3,2.8 Hz,1H),4.60(dd,J=11.3,5.3 Hz,1H),4.51(s,1H),4.33(t,J=6.2 Hz,1H),4.08(d,J=2.4 Hz,1H),3.71-3.51(m,3H),1.02(d,J=6.1 Hz,3H),0.77(d,J=6.0 Hz,3H).

[0170] Example 9 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (160 mg, 0.26 mmol) in DCM (10 mL), TFA (1.46 g, 12.8 mmol) and HO (0.5 mL) were added, and the mixture was stirred at rt for 12 h. EtN (3.0 mL) was added dropwise at 0 °C. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (90 mg, 70%). ESI-MS m / z calcd for [C 18 H 18 Cl2N4O5S2] [M+H] + :505.0;found:504.8. 1 H NMR(400 MHz,Methanol-d4)δ 8.38(s,1H),7.84(d,J=2.0 Hz,1H),7.56-7.50(m,2H),6.73(s,1H),6.19(d,J=5.6 Hz,1H),5.03(dd,J=11.2,2.8 Hz,1H),4.56(dd,J=11.2,5.2 Hz,1H),4.49-4.46(m,1H),4.19(d,J=2.0 Hz,1H),3.74-3.67(m,2H),3.40(s,3H).

[0171] Example 10 3,4-Dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 4,6-di-O-acetyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-D-galactal (25 mg, 0.066 mmol) and oxotrichloro[(dimethylsulfide)triphenylphosphine oxide]rhenium(V) (4.3 mg, 0.0066 mmol) in toluene (1 mL) was added 3,4-dichlorobenzenethiol (13 μL, 0.099 mmol), and the mixture was stirred at 70 °C for 20 h. The mixture was evaporated, and the residue was stirred in NaOMe (0.1 mL, 1 M) and MeOH (0.5 mL) at rt for 30 min. The solution was concentrated and purified by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (1.02 mg, 3%). ESI-MS m / z calculated for [C 17 H 16 Cl2N4O4S2] [M+H] + :475.0;found:475.0, 1 H NMR(400 MHz,Methanol-d4)δ 8.29(s,1H),7.78(d,J=1.9 Hz,1H),7.51(dd,J=8.4,2.0 Hz,1H),7.48(d,J=8.4 Hz,1H),6.68(s,1H),5.93(d,J=5.5 Hz,1H),5.19-5.12(m,1H),4.47(t,J=6.1 Hz,1H),4.16(s,1H),3.78-3.68(m,2H),3.09(td,J=13.6,5.9 Hz,1H),2.32(dd,J=13.3,4.1 Hz,1H).

[0172] Example 11 5-Bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (28.0 mg, 0.044 mmol) in MeOH (6.0 mL), EtN (3.0 mL), and water (1.0 mL) was stirred at rt for 3 h. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (10.3 mg, 42%). ESI-MS m / z calcd for [C 18 H 16 BrClN6O4S2] [M+H] + :559.0;found:558.9. 1 H NMR(400 MHz,Methanol-d4)δ 8.73(d,J=2.0 Hz,1H),8.67(s,1H),8.65(d,J=2.0 Hz,1H),7.50(s,1H),6.53(d,J=5.2 Hz,1H),5.16(dd,J=11.2,3.2 Hz,1H),4.73(dd,J=11.2,5.6 Hz,1H),4.43(t,J=6.0 Hz,1H),4.24(d,J=2.4 Hz,1H),3.70(d,J=6.0 Hz,2H),3.49(s,3H).

[0173] Example 12 3-Bromo-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 3-bromo-2-cyanopyridin-5-yl 4,6-di-O-acetyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (35.0 mg, 0.054 mmol) in MeOH (3.0 mL), EtN (2.0 mL), and water (1.0 mL) was stirred at rt for 3 h. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (13.3 mg, 44%). ESI-MS m / z calcd for [C 18 H 16 BrClN6O4S2] [M+H] + :559.0;found:559.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.80(d,J=2.0 Hz,1H),8.67(s,1H),8.53(d,J=2.0 Hz,1H),7.49(s,1H),6.58(d,J=5.6 Hz,1H),5.14(dd,J=11.6,2.8 Hz,1H),4.74(dd,J=11.6,5.2 Hz,1H),4.35(t,J=6.0 Hz,1H),4.20(d,J=2.4 Hz,1H),3.70(d,J=6.0 Hz,2H),3.42(s,3H).

[0174] Example 13 5-Chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (70 mg, 0.12 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 1 h, and then the pH was adjusted to pH = 8 with EtN. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO) = 20-70%, X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (25.0 mg, 42%). ESI-MS m / z calculation for [C 18 H 16 Cl2N6O4S2] [M+H] + :515.0,found:515.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.55(s,1H),8.50(d,J=2.1 Hz,1H),8.38(d,J=2.1 Hz,1H),7.37(s,1H),6.41(d,J=5.3 Hz,1H),5.04(dd,J=11.3,2.8 Hz,1H),4.63(dd,J=11.3,5.3 Hz,1H),4.31(t,J=6.0 Hz,1H),4.12(d,J=2.3 Hz,1H),3.58(t,J=10.3 Hz,2H),3.37(s,3H).

[0175] Example 14 3-Chloro-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 3-chloro-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (48 mg, 0.080 mmol) in MeOH (3.0 mL), EtN (2.0 mL), and water (1.0 mL) was stirred at rt for 3 h. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (24.5 mg, 59%). ESI-MS m / z calcd for [C 18 H 16 Cl2N6O4S2] [M+H] + :515.0;found:515.1. 1 H NMR(400 MHz,Methanol-d4)δ 8.76(d,J=2.0 Hz,1H),8.67(s,1H),8.40(d,J=1.6 Hz,1H),7.49(s,1H),6.59(d,J=5.6 Hz,1H),5.14(dd,J=11.2,2.8 Hz,1H),4.74(dd,J=11.2,5.2 Hz,1H),4.35(t,J=6.0 Hz,1H),4.20(d,J=2.0 Hz,1H),3.70-3.72(m,2H),3.42(s,3H).

[0176] Example 15 5-Chloro-2-cyanopyridin-3-yl 3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (55.0 mg, 0.091 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 1 h. The mixture was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (28.5 mg, 61%). ESI-MS m / z calcd for [C 18 H 16 Cl2N6O4S2] [M+H] + :515.0;found:515.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.51(d,J=2.0 Hz,1H),8.38(d,J=2.0 Hz,1H),8.36(s,1H),7.77(s,1H),6.42(d,J=5.2 Hz,1H),5.00(dd,J=11.2,2.8 Hz,1H),4.61(dd,J=11.2,5.2 Hz,1H),4.31(t,J=6.0 Hz,1H),4.11(d,J=2.4 Hz,1H),3.64-3.48(m,2H),3.36(s,3H).

[0177] Example 16 3,5-Dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (54.0 mg, 0.089 mmol) in DCM (5 mL), TFA (0.263 mL, 3.54 mmol) was added and the mixture was stirred at rt overnight. The mixture was evaporated and purified by column chromatography (MeCN / HO = 0 / 100 to 1 / 5, C-18 column, 20 mL / min, UV254) to give the title compound (17.9 mg, 39%). ESI-MS m / z calculation for [C 18 H 18 Cl2FN5O4S2] [M+H] + :522.0;found:522.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.23(s,1H),7.75(d,J=6.3 Hz,2H),6.95(s,1H),6.16(d,J=5.3 Hz,1H),4.97(dd,J=11.3,2.6 Hz,1H),4.55(dd,J=11.4,5.3 Hz,1H),4.45(t,J=6.2 Hz,1H),4.17(s,1H),3.77-3.63(m,2H),3.38(s,3H).

[0178] Example 17 5-Chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene 3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (75 mg, 0.13 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 3 h, after which the pH was adjusted to 8 using EtN. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO) = 0-60%, X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (26.4 mg, 42%). ESI-MS m / z calculation for [C 18 H 18 ClN7O4S2] [M+H] + :496.1,found:496.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.50(d,J=2.2 Hz,1H),8.38(d,J=2.2 Hz,1H),8.16(s,1H),6.87(s,1H),6.41(d,J=5.3 Hz,1H),4.96(dd,J=11.3,2.9 Hz,1H),4.56(dd,J=11.3,5.3 Hz,1H),4.29(t,J=6.0 Hz,1H),4.09(d,J=2.5 Hz,1H),3.58(d,J=6.1 Hz,2H),3.37(d,J=12.0 Hz,3H).

[0179] Example 18 5-Chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (85 mg, 0.14 mmol) in DCM (10 mL) was added TFA (820 mg, 7.19 mmol) and HO (0.5 mL), and the mixture was stirred at rt for 12 h. EtN (3.0 mL) was added dropwise at 0 °C, and the mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (25 mg, 36%). ESI-MS m / z calculation for [C 18 H 21 ClN6O4S2] [M+H] + :485.1;found:485.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.30(d,J=2.4 Hz,1H),8.26(s,1H),8.20(d,J=2.4 Hz,1H),6.97(s,1H),6.30(d,J=5.2Hz,1H),5.06(dd,J=11.6,2.8 Hz,1H),4.73-4.56(m,1H),4.39(t,J=6.4 Hz,1H),4.19(d,J=2.4 Hz,1H),3.82-3.58(m,2H),3.40(s,3H),2.66(s,3H).

[0180] Example 19 5-Chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (98.0 mg, 0.15 mmol) in DCM / TFA (6 mL, 5:1) was stirred at rt for 3 h. The mixture was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (17.8 mg, 21%). ESI-MS m / z calcd for [C 24 H 22 ClN7O4S2] [M+H] + :572.1;found:572.2. 1 H NMR(400 MHz,Methanol-d4)δ 8.61(d,J=2.4 Hz,1H),8.42(d,J=2.4 Hz,1H),8.12(s,1H),7.24-7.09(m,5H),6.97(s,1H),6.36(d,J=5.2 Hz,1H),5.12(dd,J=11.2,2.8 Hz,1H),4.82-4.71(m,2H),4.63(s,1H),4.51(d,J=11.2 Hz,1H),4.41(t,J=6.0 Hz,1H),4.20(d,J=2.4 Hz,1H),3.72-3.63(m,2H).

[0181] Example 20 5-Chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (115 mg, 0.15 mmol) in DCM (10 mL) was added TFA (860 mg, 7.54 mmol) and HO (0.5 mL), and the mixture was stirred at rt for 12 h. EtN (3.0 mL) was added dropwise at 0 °C, and the mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (42 mg, 56%). ESI-MS m / z calculation for [C 19 H 23 ClN6O4S2] [M+H] + :499.1;found:499.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.30(d,J=2.4 Hz,1H),8.26(s,1H),8.18(d,J=2.4 Hz,1H),6.97(s,1H),6.26(d,J=5.2 Hz,1H),5.07(dd,J=11.6,2.8 Hz,1H),4.70(dd,J=11.6,5.3 Hz,1H),4.48-4.33(m,1H),4.20(d,J=2.4 Hz,1H),3.84-3.61(m,3H),3.51-3.35(m,1H),2.65(s,3H),1.03(t,J=7.0 Hz,3H).

[0182] Example 21 5-Chloro-2-(pyrimidin-5-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(pyrimidin-5-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (70 mg, 0.11 mmol) in DCM / TFA (10.0 mL, 19:1) was stirred at rt for 1 h. The mixture was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (27 mg, 45%). ESI-MS m / z calculation for [C 21 H 21 ClN8O4S2] [M+H] + :549.1;found:549.1. 1 H NMR(400 MHz,Methanol-d4)δ 9.13(s,1H),9.06(s,2H),8.54(d,J=2.0 Hz,1H),8.36(d,J=2.0 Hz,1H),8.11(s,1H),6.85(s,1H),6.00(d,J=4.8 Hz,1H),4.80-4.70(s,1H),4.41(d,J=5.6 Hz,1H),4.13(t,J=5.6 Hz,1H),4.01(s,1H),3.56(d,J=6.0 Hz,2H),3.07(s,3H).

[0183] Example 22 5-Chloro-2-(pyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(pyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (70.0 mg, 0.11 mmol) in DCM (10 mL) was added TFA (0.409 mL, 5.50 mmol), and the mixture was stirred at rt for 2 h. EtN (1 mL) was added at 0 °C, and the mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (33.0 mg, 55%). ESI-MS m / z calculation for [C 22 H 22 ClN7O4S2] [M+H] + :548.1;found:547.9. 1 H NMR(400 MHz,Methanol-d4)δ 8.89-8.54(m,3H),8.45(d,J=2.0 Hz,1H),8.21(s,1H),7.89-7.68(m,2H),7.10-6.85(m,1H),6.11(d,J=5.2 Hz,1H),4.90-4.87(m,1H),4.58-4.46(m,1H),4.25(t,J=6.0 Hz,1H),4.13(s,1H),3.73-3.58(m,2H),3.16(s,3H).

[0184] Example 23 5-Chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (68 mg, 0.12 mmol) in DCM / TFA (6 mL, 5:1) was stirred at rt for 3 h and then neutralized with EtN. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (32.8 mg, 56%). ESI-MS m / z calcd for [C 22 H 22 ClN7O4S2] [M+H] + :548.1;found:548.2. 1 H NMR(400 MHz,DMSO-d6)δ 8.83(s,1H),8.65(d,J=2.4 Hz,2H),8.41(d,J=1.6 Hz,1H),8.11-8.05(m,2H),7.56(q,J=7.6,4.8 Hz,1H),7.07(s,2H),6.89(s,1H),6.27(d,J=5.2 Hz,1H),5.52(d,J=6.4 Hz,1H),4.76-4.71(m,2H),4.52(dd,J=11.6,5.2 Hz,1H),4.07(t,J=6.4 Hz,1H),3.96(q,J=6.4,2.4 Hz,1H),3.53-3.47(m,1H),3.41-3.36(m,1H),3.08(s,3H).

[0185] Example 24 5-Chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (40 mg, 0.094 mmol) in DMF (2 mL) was added 4-(2-trimethylsilylethynyl)thiazol-2-amine (20.2 mg, 0.10 mmol), sodium (+)-L-ascorbate (18.5 mg, 0.094 mmol), copper(II) sulfate pentahydrate (23.3 mg, 0.094 mmol), and CsF (21.3 mg, 0.14 mmol), and the mixture was stirred at rt overnight. The mixture was filtered, and the filtrate was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (8.0 mg, 16%). ESI-MS m / z calcd for [C 22 H 26 ClN7O4S2] [M+H] + :552.1;found:551.8. 1 H NMR(400 MHz,Methanol-d4)δ 8.55-8.04(m,3H),7.10-6.81(m,1H),6.37-6.22(m,1H),6.14-5.99(m,1H),5.12-5.01(m,1H),4.68-4.53(m,1 H),4.43-4.28(m,1H),4.25-4.14(m,1H),3.85-3.57(m,4H),3.37(s,3H),3.23-3.14(m,2H),2.76-2.49(m,2H).

[0186] Example 25 5-Chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-(3,5-difluoro-4-(4-methoxybenzyloxy)benzyl)-1-thio-α-D-galactopyranoside (60 mg, 0.071 mmol) in DCM (3 mL) was added TFA (248 mg, 2.16 mmol) and HO (0.5 mL), and the mixture was stirred at rt for 12 h. EtN (1.0 mL) was added dropwise at 0 °C, and the mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (33 mg, 73%). ESI-MS m / z calcd for [C 24 H 20 ClF2N7O5S2] [M+H] + :624.1;found:624.1. 1 H NMR(400 MHz,Methanol-d4)δ 8.51(d,J=2.0 Hz,1H),8.34(d,J=2.0 Hz,1H),8.04(s,1H),6.87(s,1H),6.62-6.54(m,2H),6.29(d,J=5.2 Hz,1H),5.01(dd,J=11.2,2.8 Hz,1H),4.70(dd,J=11.2,5.2 Hz,1H),4.56(d,J=11.6 Hz,1H),4.33-4.26(m,2H),4.10(d,J=2.4 Hz,1H),3.63-3.55(m,2H).

[0187] Example 26 5-Chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (35.0 mg, 0.055 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 1 h. The mixture was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (14.5 mg, 48%). ESI-MS m / z calcd for [C 22 H 22 ClN7O4S2] [M+H] + :548.1;found:548.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.58(d,J=4.4 Hz,1H),8.42(d,J=2.4 Hz,1H),8.36(d,J=2.4 Hz,1H),8.09(s,1H),7.89(td,J=7.6,1.6 Hz,1H),7.75(d,J=7.6 Hz,1H),7.41(ddd,J=7.6,5.2,0.8 Hz,1H),6.83(s,1H),6.09(d,J=5.2 Hz,1H),4.78(m,1H),4.41(dd,J=11.2,5.2 Hz,1H),4.18(t,J=6.0 Hz,1H),4.01(d,J=2.4 Hz,1H),3.65-3.50(m,2H),3.08(s,3H).

[0188] Example 27 5-Chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(oxazol-2-yl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(N-tert-butoxycarbonyl-2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (120 mg, 0.22 mmol) in DCM (5 mL) was added TFA (528 mg, 4.63 mmol) and HO (0.5 mL), and the mixture was stirred at rt for 12 h. EtN (1.5 mL) was added dropwise at 0 °C, and the mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (16 mg, 26%). ESI-MS m / z calcd for [C 20 H 20 ClN7O5S2] [M+H] + :538.1;found:538.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.43(d,J=2.0 Hz,1H),8.38(d,J=2.0 Hz,1H),8.15(s,1H),8.03(s,1H),7.36(s,1H),6.86(s,1H),6.39(d,J=5.6 Hz,1H),4.98(dd,J=11.2,2.8 Hz,1H),4.53(dd,J=11.2,5.2 Hz,1H),4.25-4.22(m,1H),4.07(d,J=2.4 Hz,1H),3.60-3.53(m,2H),3.26(s,3H).

[0189] Example 28 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 3,4-dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (90.0 mg, 0.15 mmol) in DCM / TFA (10.0 mL, 19:1) was stirred at rt for 1 h. The mixture was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (37.5 mg, 49%). ESI-MS m / z calcd for [C 18 H 19 Cl2N5O4S2] [M+H] + :504.0;found:504.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.25(s,1H),7.81(d,J=2.0 Hz,1H),7.54(dd,J=8.4,2.0 Hz,1H),7.47(d,J=8.4 Hz,1H),6.96(s,1H),6.16(d,J=5.2 Hz,1H),4.98(dd,J=11.2,1.6 Hz,1H),4.55(dd,J=11.2,5.2 Hz,1H),4.45(t,J=6.4 Hz,1H),4.18(s,1H),3.69(qd,J=11.6,6.4 Hz,2H),3.37(s,3H).

[0190] Example 29 5-Chloro-2-(thiazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(thiazol-2-yl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(N-tert-butoxycarbonyl-2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (50 mg, 0.033 mmol) in DCM (5 mL) was added TFA (192 mg, 1.68 mmol) and HO (0.5 mL), and the mixture was stirred at rt for 12 h. EtN (1.5 mL) was added dropwise at 0 °C, and the mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (2.7 mg, 14%). ESI-MS m / z calcd for [C 20 H 20 ClN7O4S3] [M+H] + :554.0;found:554.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.44(dd,J=6.8,2.0 Hz,2H),8.27(s,1H),8.02(d,J=3.2 Hz,1H),7.71(d,J=3.2 Hz,1H),6.98(s,1H),6.52(d,J=5.6 Hz,1H),5.15(dd,J=11.2,2.8 Hz,1H),4.66(dd,J=11.2,5.2 Hz,1H),4.38-4.35(m,1H),4.19(d,J=2.8 Hz,1H),3.74-3.64(m,2H),3.38(s,3H).

[0191] Example 30 3-Chloro-4-(trifluoromethyl)phenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 3-chloro-4-(trifluoromethyl)phenyl 4,6-O-benzylidene-3-[4-(N-tert-butoxycarbonyl-2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (260 mg, 0.35 mmol) in DCM / TFA (20 mL, 19:1) was stirred at rt for 6 h. The mixture was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (102 mg, 54%). ESI-MS m / z calcd for [C 19 H 19 ClF3N5O4S2] [M+H] + :538.1;found:538.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.27(s,1H),7.88(s,1H),7.72(d,J=7.6 Hz,2H),6.98(s,1H),6.41(d,J=5.6 Hz,1H),5.02(dd,J=11.6,2.8 Hz,1H),4.62(dd,J=11.2,5.2 Hz,1H),4.43-4.40(m,1H),4.20(d,J=2.0 Hz,1H),3.76-3.66(m,2H),3.40(s,3H).

[0192] Example 31 3-Chlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3-chlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (70 mg, 0.13 mmol) in DCM (10 mL) was added TFA (0.409 mL, 5.50 mmol), and the mixture was stirred at rt for 2 h. EtN (1 mL) was added at 0 °C, and the mixture was concentrated. The residue was purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (16.0 mg, 27%). ESI-MS m / z calcd for [C 18 H 20 ClN5O4S2] [M+H] + :470.1;found:470.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.24(s,1H),7.70-7.65(m,1H),7.60-7.51(m,1H),7.36-7.28(m,2H),6.96(s,1H),6.15(d,J=5.2 Hz,1H),4.99(dd,J=11.2,2.8 Hz,1H),4.56(dd,J=11.2,5.2 Hz,1H),4.48(t,J=6.0 Hz,1H),4.19(d,J=2.4 Hz,1H),3.69(ddd,J=26.4,11.2,6.0 Hz,2H),3.38(s,3H).

[0193] Example 32 3,5-Dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 3,5-dichloro-4-fluorophenyl 2,4,6-tri-O-acetyl-3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (75 mg, 0.12 mmol) in MeOH (5.0 mL), EtN (2.49 mL, 17.9 mmol), and water (829 mg, 46 mmol) was stirred at rt overnight. The mixture was concentrated and purified by column chromatography (MeCN / HO = 1 / 20 to 1 / 7, C-18 column, 20 mL / min, UV254) to give the title compound (36.0 mg, 60%). ESI-MS m / z calculation for [C 17 H 16 Cl2FN5O4S2] [M+H] + :508.0;found:508.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.13(s,1H),7.63(d,J=6.3 Hz,2H),6.86(s,1H),5.72(d,J=5.2 Hz,1H),4.85(dd,J=11.4,2.7 Hz,1H),4.78(m,1H),4.38(t,J=6.0 Hz,1H),4.08(s,1H),3.68-3.55(m,2H).

[0194] Example 33 3-Bromo-2-(trifluoromethyl)pyridin-5-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 3-bromo-2-(trifluoromethyl)pyridin-5-yl 2,4,6-tri-O-acetyl-3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (13.0 mg, 0.018 mmol) in MeOH / EtN / HO (9 mL, 5:3:1) was stirred overnight at rt. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (8.70 mg, 71%). ESI-MS m / z calcd for [C 18 H 18 BrF3N6O4S2] [M+H] + :583.0;found:583.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.74(d,J=1.6 Hz,1H),8.50(d,J=1.6 Hz,1H),8.19(s,1H),6.11(d,J=5.6 Hz,1H),5.02(dd,J=11.2,2.8 Hz,1H),4.95-4.91(m,1H),4.39(t,J=6.0 Hz,1H),4.18(d,J=2.0 Hz,1H),3.75-3.57(m,2H),2.52(s,3H).

[0195] Example 34 5-Bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (52.0 mg, 0.084 mmol) in MeOH (3.0 mL), EtN (2.0 mL), and water (1.0 mL) was stirred at rt for 4 h. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (34.0 mg, 76%). ESI-MS m / z calcd for [C 19 H 19 BrN6O4S2] [M+H] + :539.0;found:539.1. 1 H NMR(400 MHz,Methanol-d4)δ 8.73(d,J=2.0 Hz,1H),8.65(d,J=2.0 Hz,1H),8.61(s,1H),7.20(d,J=0.8 Hz,1H),6.53(d,J=5.2 Hz,1H),5.15(dd,J=11.2,2.8 Hz,1H),4.74-4.70(m,1H),4.43(t,J=6.0 Hz,1H),4.23(d,J=2.4 Hz,1H),3.70(d,J=6.0 Hz,2H),3.49(s,3H),2.49(s,3H).

[0196] Example 35 2-Cyano-5-methylpyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 2-cyano-5-methylpyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (95.0 mg, 0.16 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 6 h. EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (58.0 mg, 75%). ESI-MS m / z calcd for [C 20 H 22 N6O4S2] [M+H] + :475.1;found:475.2. 1 H NMR(400 MHz,Methanol-d4)δ 8.58(s,1H),8.46(dd,J=2.0,0.8 Hz,1H),8.20(dd,J=2.0,0.8 Hz,1H),7.17(d,J=0.8 Hz,1H),6.37(d,J=5.2 Hz,1H),5.12(dd,J=11.2,2.8 Hz,1H),4.67(dd,J=11.2,5.2 Hz,1H),4.47(t,J=6.0 Hz,1H),4.21(d,J=2.4 Hz,1H),3.67(d,J=6.0 Hz,2H),3.47(s,3H),2.47(s,3H),2.44(s,3H).

[0197] Example 36 2-Cyano-5-methylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 2-cyano-5-methylpyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (220 mg, 0.37 mmol) in DCM / TFA (20 mL, 19:1) was stirred at rt for 6 h. EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (95.0 mg, 51%). ESI-MS m / z calcd for [C 19 H 19 ClN6O4S2] [M+H] + :495.1;found:495.2. 1 H NMR(400 MHz,Methanol-d4)δ 8.64(s,1H),8.45(d,J=1.6 Hz,1H),8.20(dd,J=1.6,0.8 Hz,1H),7.46(s,1H),6.36(d,J=5.2 Hz,1H),5.12(dd,J=11.2,3.2 Hz,1H),4.69(dd,J=11.2,2.8 Hz,1H),4.46(t,J=6.0 Hz,1H),4.21(d,J=2.4 Hz,1H),3.67(d,J=6.0 Hz,2H),3.47(s,3H),2.44(s,3H).

[0198] Example 37 5-Ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (35 mg, 0.055 mmol) in DCM (6 mL) was added TFA (0.406 mL, 5.47 mmol), and the mixture was stirred at rt overnight. EtN (1 mL) was added at 0 °C to neutralize the TFA, and the mixture was concentrated. The residue was dissolved in DMF (3 mL), KF (6.35 mg, 0.11 mmol) was added, and the mixture was stirred at rt for 1 h. The mixture was filtered and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (13.5 mg, 52%). ESI-MS m / z calcd for [C 19 H 18 ClN5O4S2] [M+H] + :480.0;found:480.2. 1 H NMR(400 MHz,Methanol-d4)δ 8.70(d,J=2.0 Hz,1H),8.63(s,1H),8.54(d,J=1.6 Hz,1H),8.20(t,J=2.0 Hz,1H),7.46(s,1H),6.24(d,J=5.2 Hz,1H),5.08(dd,J=11.2,2.8 Hz,1H),4.63(dd,J=11.2,5.2 Hz,1H),4.47(t,J=6.0 Hz,1H),4.20(d,J=2.4 Hz,1H),3.76-3.57(m,2H),3.41(s,3H).

[0199] Example 38 5-Chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptanyl}pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptanyl}pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (120 mg, 0.18 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 1 h. EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (39.6 mg, 38%). ESI-MS m / z calculation for [C 22 H 26 ClN7O5S2] [M+H] + :568.1;found:568.0. 1 H NMR(400 MHz,DMSO-d6)δ 8.18(s,1H),8.08(d,J=2.4 Hz,1H),7.85(d,J=2.4 Hz,1H),7.10(s,2H),6.92(s,1H),6.04(d,J=5.2 Hz,1H),5.52(d,J=6.8 Hz,1H),4.87(dd,J=11.6,2.0Hz,1H),4.77(t,J=5.2 Hz,1H),4.74-4.62(m,4H),4.53(dd,J=11.2,5.2 Hz,1H),4.36(d,J=9.2 Hz,2H),4.29(d,J=9.2 Hz,2H),4.25(t,J=6.0 Hz,1H),4.03(d,J=3.6 Hz,1H),3.57-3.49(m,1H),3.40(dd,J=11.6,6.0 Hz,1H),3.29(s,3H).

[0200] Example 39 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 3-chloro-4-cyanophenyl 4,6-di-O-acetyl-3-[4-(2-aminotriazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (25 mg, 0.043 mmol) in MeOH (5.0 mL), EtN (3.0 mL), and water (1.0 mL) was stirred overnight at rt. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (8.8 mg, 41%). ESI-MS m / z calcd for [C 19 H 19 ClN6O4S2] [M+H] + :495.1;found:495.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.24(s,1H),7.88(d,J=1.2 Hz,1H),7.74-7.63(m,2H),6.95(s,1H),6.45(d,J=5.2 Hz,1H),5.00(dd,J=11.6,2.8 Hz,1H),4.61(dd,J=11.6,5.2 Hz,1H),4.34(t,J=6.0 Hz,1H),4.17(d,J=2.4 Hz,1H),3.77-3.62(m,2H),3.36(s,3H).

[0201] Example 40 5-Cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-cyanopyridin-3-yl 4,6-O-benzylidene-3-{4-[2-(di-tert-butoxycarbonylamino)thiazol-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (110 mg, 0.15 mmol) in DCM / TFA (10 mL, 19:1) was stirred overnight at rt. The mixture was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (40.2 mg, 59%). ESI-MS m / z calcd for [C 18 H 19 N7O4S2] [M+H] + :462.1;found:462.1. 1 H NMR(400 MHz,Methanol-d4)δ 8.95(d,J=2.4 Hz,1H),8.79(d,J=2.0 Hz,1H),8.49(t,J=2.0 Hz,1H),8.24(s,1H),6.95(s,1H),6.33(d,J=5.6 Hz,1H),5.03(dd,J=11.2,2.8 Hz,1H),4.59(dd,J=11.2,5.6 Hz,1H),4.42(t,J=6.0 Hz,1H),4.17(d,J=2.4 Hz,1H),3.68(d,J=6.0 Hz,2H),3.39(s,3H).

[0202] Example 41 3,5-Dichloro-4-fluorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] HBr (1 mL) was added to a suspension of 4,6-di-O-acetyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-D-galactal (400 mg, 1.05 mmol) in THF (20 mL), and the mixture was stirred at rt for 22 h. Water (10 mL) was added, followed by Na2CO3 (446 mg, 4.21 mmol), and the mixture was stirred at rt for 30 min. The mixture was concentrated and stirred in pyridine (10 mL) and acetic anhydride (10 mL) at rt for 24 h. The mixture was concentrated and partitioned between EtOAc and water. The organic phase was dried, evaporated, and purified by chromatography (SiO2, PE / EtOAc) to give crude acetyl 3-[4-(2-acetoxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-di-O-acetyl-2,3-dideoxy-D-galactopyranoside. A solution of 5-benzylsulfanyl-1,3-dichloro-2-fluorobenzene (327 mg, 1.14 mmol) in toluene (2.5 mL) was added to a cooled (0 °C) suspension of AlCl3 (258 g, 1.94 mmol) in toluene (7.5 mL). The resulting mixture was allowed to reach rt in 15 min and then stirred at rt for 2 h. The mixture was cooled to 0 °C and quenched by the addition of water. The phases were separated, and the organic phase was washed with water, dried, and concentrated. The residue and crude acetyl 3-[4-(2-acetoxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-di-O-acetyl-2,3-dideoxy-D-galactopyranoside were dissolved in DCM (6 mL). Boron trifluoride diethyl etherate (0.11 mL, 0.91 mmol) was added, and the mixture was stirred at rt for 16 h. The mixture was diluted with DCM and washed with saturated aqueous NaHCO3. The aqueous phase was extracted with EtOAc, and the combined organic phases were dried and evaporated. The residue was stirred with MeOH (3 mL), Et3N (1 mL), and HO (0.5 mL) at rt for 28 h. The mixture was evaporated and purified by preparative HPLC (C 18 , HO / MeCN / 0.1% TFA) to give the title compound (6.6 mg, 1.3%). ESI-MS m / z calculated for [C 17 H 15Cl2FN4O4S2] [M+H] + :493.0;found:492.7, 1 H NMR(500 MHz,Methanol-d4)δ 8.31(s,1H),7.73(d,J=6.2 Hz,2H),6.70(s,1H),5.93(d,J=5.5 Hz,1H),5.17(ddd,J=13.6,3.9,2.5 Hz,1H),4.50(t,J=6.1 Hz,1H),4.17(d,J=2.2 Hz,1H),3.76(d,J=6.0 Hz,2H),3.10(td,J=13.5,5.8 Hz,1H),2.33(dd,J=13.4,4.3 Hz,1H).

[0203] Example 42 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside [ka] HBr (0.12 mL) was added to a solution of 4,6-di-O-acetyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-D-galactal (100 mg, 0.26 mmol) in THF (7.5 mL), and the mixture was stirred at rt for 3 h. Water (2.5 mL) was added, followed by Na2CO3 (56 mg, 0.53 mmol), and the mixture was stirred at rt for 40 min. The mixture was concentrated and stirred in pyridine (3 mL) and acetic anhydride (3 mL) at rt for 2 h. The mixture was concentrated and partitioned between EtOAc and water. The organic phase was dried, evaporated, and purified by chromatography (SiO2, PE / EtOAc). The resulting material was dissolved in DCM (3 mL) along with 2-chloro-4-sulfanylbenzonitrile (53 mg, 0.31 mmol). Boron trifluoride diethyl etherate (0.10 mL, 0.83 mmol) was added and the mixture was stirred at rt for 18 h. The mixture was diluted with DCM and washed with saturated aqueous NaHCO3. The organic phase was dried and evaporated, and the residue was stirred in methylamine (40% in MeOH, 2 mL) at 50 °C for 50 h. The mixture was evaporated and analyzed by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (21 mg, 17%). ESI-MS m / z calculated for [C 18 H 17 ClN6O3S2] [M+H] + :465.0;found:464.8, 1 H NMR(400 MHz,Methanol-d4)δ 8.42(s,1H),7.85(d,J=1.5 Hz,1H),7.71(d,J=8.2 Hz,1H),7.64(dd,J=8.2,1.6 Hz,1H),7.09(s,1H),6.19(d,J=5.6 Hz,1H),5.20(dt,J=13.6,3.4 Hz,1H),4.39(t,J=6.1 Hz,1H),4.18(s,1H),3.78-3.70(m,2H),3.16(td,J=13.5,5.6 Hz,1H),2.35(dd,J=13.6,4.1 Hz,1H).

[0204] Example 43 5-Chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside [ka] HBr (0.075 mL) was added to a solution of 4,6-di-O-acetyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-D-galactal (100 mg, 0.25 mmol) in THF (5 mL), and the mixture was stirred at rt for 3 h. Water (2.5 mL) was added, followed by Na2CO3 (53 mg, 0.50 mmol), and the mixture was stirred at rt for 20 min. The mixture was extracted with EtOAc and washed with water. The organic phase was dried, evaporated, and purified by chromatography (SiO2, PE / EtOAc). The resulting material was dissolved in DCM (5 mL) along with 4-chloro-2-sulfanylbenzonitrile (39 mg, 0.23 mmol). Trifluoromethanesulfonic acid (41 μL, 0.46 mmol) was added, and the mixture was stirred at rt for 1 h. The mixture was diluted with DCM and washed with saturated aqueous NaHCO3. The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in MeOH (4 mL) and NaOMe (0.5 mL, 1 M) at rt for 20 min. The mixture was concentrated and purified by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (11 mg, 9%). ESI-MS m / z calculated for [C 18 H 15 Cl2N5O3S2] [M+H] + :484.0;found:484.0, 1H NMR(400 MHz,Methanol-d4)δ 8.58(s,1H),8.02(d,J=2.0 Hz,1H),7.74(d,J=8.4 Hz,1H),7.50-7.44(m,2H),6.16(d,J=5.5 Hz,1H),5.26(d,J=13.0 Hz,1H),4.46(t,J=6.0 Hz,1H),4.23(s,1H),3.79-3.68(m,2H),3.22(td,J=13.5,5.8 Hz,1H),2.45(dd,J=13.7,4.5 Hz,1H).

[0205] Example 44 3-Cyano-2-(trifluoromethyl)pyridin-5-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3-cyano-2-(trifluoromethyl)pyridin-5-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (52 mg, 0.11 mmol), CuI (2.0 mg, 0.11 mmol), and tert-butyl N-[4-(2-trimethylsilylethynyl)thiazol-2-yl]carbamate (38 mg, 0.13 mmol) in MeCN (1.0 mL) was added TBAF (106 μL, 1 M in THF, 0.11 mmol), and the mixture was stirred at rt for 5 h. The mixture was diluted with EtOAc (20 mL) and washed with water (3 × 10 mL) and brine (10 mL). The organic phase was dried and evaporated. The residue was dissolved in DCM (2 mL) and TFA (0.2 mL) and stirred at rt for 16 h. The mixture was evaporated and the residue was stirred in MeOH (2 mL) and NaOMe (0.11 mL, 1 M) at rt for 20 min. Acetic acid (20 μL) was added and the mixture was concentrated and purified by preparative HPLC (C 18 , HO / MeCN / 0.1% TFA) to give the title compound as a TFA salt (23 mg, 34%). ESI-MS m / z calcd for [C19 H 18 F3N7O4S2] [M+H] + :530.1;found:529.9, 1 H NMR(400 MHz,Methanol-d4)δ 9.03(d,J=2.0 Hz,1H),8.68(d,J=2.0 Hz,1H),8.26(s,1H),6.97(s,1H),6.57(d,J=5.3 Hz,1H),5.06(dd,J=11.2,2.7 Hz,1H),4.64(dd,J=11.3,5.3 Hz,1H),4.35(dd,J=7.1,4.7 Hz,1H),4.17(d,J=2.4 Hz,1H),3.78-3.63(m,2H),3.40(s,3H).

[0206] Example 45 5-Chloro-2-(N-azetidinylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(N-azetidinylcarbamoyl)-3-pyridyl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (51 mg, 0.12 mmol), CuI (28 mg, 0.15 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (38 mg, 0.18 mmol) in MeCN (1.5 mL) was added DIPEA (61 μL, 0.36 mmol), and the mixture was stirred at 50 °C for 2 h. The mixture was analyzed by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (48 mg, 71%). ESI-MS m / z calcd for [C 21 H 22 Cl2N6O5S2] [M+H] + :573.0;found:572.8. 1H NMR(400 MHz,Methanol-d4)δ 8.63(s,1H),8.48(d,J=2.1 Hz,1H),8.38(d,J=2.1 Hz,1H),7.47(d,J=2.7 Hz,1H),6.36(d,J=5.4 Hz,1H),5.11(dd,J=11.3,2.9 Hz,1H),4.66(dd,J=11.4,5.4 Hz,1H),4.44(t,J=6.0 Hz,1H),4.27-4.16(m,5H),3.74-3.64(m,2H),3.41(s,3H),2.39(p,J=7.8 Hz,2H).

[0207] Example 46 5-Chloro-2-(pyridin-2-yl)pyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (76 mg, 0.18 mmol), CuI (43 mg, 0.22 mmol), and trimethyl-[2-(4-methylthiazol-2-yl)ethynyl]silane (44 mg, 0.22 mmol) in MeCN (2.0 mL) was added DIPEA (92 μL, 0.54 mmol), and the mixture was stirred at 50 °C for 2 h. The mixture was concentrated and partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried, evaporated, and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA) to give the title compound (41 mg, 42%). ESI-MS m / z calcd for [C 23 H 23 ClN6O4S2] [M+H] + :547.1;found:547.1. 1H NMR(500 MHz,Methanol-d4)δ 8.80(d,J=5.0 Hz,1H),8.62(d,J=2.1 Hz,1H),8.55-8.52(m,2H),8.29(td,J=7.8,1.6 Hz,1H),8.22(d,J=7.9 Hz,1H),7.79-7.74(m,1H),7.18(d,J=1.0 Hz,1H),6.25(d,J=5.3 Hz,1H),4.98(dd,J=11.4,2.9 Hz,1H),4.58(dd,J=11.4,5.3 Hz,1H),4.24(t,J=6.1 Hz,1H),4.13(d,J=2.3 Hz,1H),3.70-3.64(m,2H),3.23(s,3H),2.47(d,J=0.9 Hz,3H).

[0208] Example 47 5-Ethynylpyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a nitrogen-purged solution of 5-bromopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (30 mg, 0.60 mmol), CuI (0.6 mg, 0.003 mmol), and bis(triphenylphosphine)palladium(II) chloride (2.1 mg, 0.003 mmol) in THF (0.75 mL) was added ethynyl(trimethyl)silane (11.6 μL, 0.084 mmol) followed by DIPEA (14.6 μL, 0.084 mmol), and the mixture was stirred at 50° C. for 20 h. The mixture was cooled to rt, and TBAF (0.15 mL, 1 M in THF, 0.15 mmol) was added. After stirring at rt for 30 min, the mixture was partitioned between EtOAc and water. The organic phase was dried, evaporated and purified by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (14 mg, 52%). ESI-MS m / z calcd for [C19 H 19 N5O4S2] [M+H] + :446.1;found:446.1. 1 H NMR(400 MHz,Methanol-d4)δ 8.65(d,J=1.9 Hz,1H),8.51(s,1H),8.48(s,1H),8.18(t,J=2.0 Hz,1H),7.79(d,J=3.0 Hz,1H),7.54(d,J=3.1 Hz,1H),6.19(d,J=5.3 Hz,1H),4.99(dd,J=11.3,2.8 Hz,1H),4.54(dd,J=11.3,5.3 Hz,1H),4.36(t,J=6.0 Hz,1H),4.11(d,J=2.2 Hz,1H),3.80(s,1H),3.64-3.54(m,2H),3.31(d,J=2.0 Hz,3H).

[0209] Example 48 5-Chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (92 mg, 0.20 mmol), CuI (7.6 mg, 0.04 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (52 mg, 0.24 mmol) in MeCN (2.0 mL) was added EtN (0.11 mL, 0.80 mmol) and TBAF (0.02 mL, 1 M in THF, 0.020 mmol), and the mixture was stirred at 50 °C for 90 min. The mixture was filtered through a celite plug and concentrated. The residue was stirred in MeOH (1 mL), EtN (0.45 mL), and water (0.15 mL) at rt for 16 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18, HO / MeCN / 0.1%TFA) to give the title compound (61 mg, 64%). ESI-MS m / z calculated for [C 16 H 15 Cl2N5O4S2] [M+H] + :476.0;found:476.0. 1 H NMR(500 MHz,Methanol-d4)δ 8.68(s,1H),8.62(s,1H),8.51(s,1H),8.24(t,J=2.0 Hz,1H),7.48(s,1H),5.96(d,J=5.4 Hz,1H),5.09(dd,J=11.4,2.9 Hz,1H),4.96(dd,J=11.4,5.4 Hz,1H),4.50(t,J=6.1 Hz,1H),4.24(d,J=2.0 Hz,1H),3.77-3.68(m,2H).

[0210] Example 49 5-Bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of sodium (+)-L-ascorbate (59 mg, 0.30 mmol) and copper(II) sulfate pentahydrate (37 mg, 0.15 mmol) in water (2.5 mL) was added to a solution of 5-bromopyridin-3-yl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (745 mg, 1.48 mmol), 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (479 mg, 2.22 mmol), and KCO (2.05 g, 14.8 mmol) in MeOH / THF (35 mL, 1:1), and the mixture was stirred at rt for 16 h and then at 50 °C for 24 h. The mixture was concentrated and partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc, and the combined organic phases were dried and evaporated. The residue was suspended in DCM and the solid was filtered off to give the title compound (589 mg, 76%). ESI-MS m / z calcd for [C16 H 15 BrClN5O4S2] [M+H] + :519.9;found:519.9. 1 H NMR(400 MHz,Methanol-d4)δ 8.69(d,J=1.8 Hz,1H),8.60(s,1H),8.58(d,J=2.1 Hz,1H),8.36(t,J=2.0 Hz,1H),7.47(s,1H),5.93(d,J=5.4 Hz,1H),5.07(dd,J=11.4,2.9 Hz,1H),4.93(dd,J=11.4,5.4 Hz,1H),4.48(t,J=6.1 Hz,1H),4.21(d,J=2.0 Hz,1H),3.76-3.66(m,2H).

[0211] Example 50 5-Chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 4-chloro-2-cyanophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (125 mg, 0.26 mmol), CuI (9.9 mg, 0.052 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (67 mg, 0.31 mmol) in MeCN (2.0 mL) was added EtN (0.14 mL, 1.04 mmol) and TBAF (26 μL, 1 M in THF, 0.026 mmol), and the mixture was stirred at 50° C. for 90 min. The mixture was filtered and concentrated, and the residue was stirred in MeOH (2 mL), EtN (0.3 mL), and water (0.1 mL) at 50° C. for 16 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA). The resulting material was filtered through an SCX column to give the title compound (93 mg, 72%). ESI-MS m / z calcd for [C 16 H 15Cl2N5O4S2] [M+H] + :500.0;found:500.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.61(s,1H),7.98(d,J=1.9 Hz,1H),7.74(d,J=8.3 Hz,1H),7.51-7.43(m,2H),6.13(d,J=5.3 Hz,1H),5.11(dd,J=11.3,2.8 Hz,1H),4.98(dd,J=11.4,5.4 Hz,1H),4.42(t,J=6.2 Hz,1H),4.28-4.21(m,1H),3.70(dd,J=11.4,5.6 Hz,1H),3.64(dd,J=11.4,6.6 Hz,1H).

[0212] Example 51 3-Chloro-5-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 3-chloro-5-cyanophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (80 mg, 0.17 mmol), CuI (6.3 mg, 0.033 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (43 mg, 0.20 mmol) in MeCN (1.3 mL) was added EtN (92 μL, 0.66 mmol) and TBAF (17 μL, 1 M in THF, 0.017 mmol), and the mixture was stirred at 50° C. for 1 h. The mixture was filtered and concentrated, and the residue was stirred in MeOH (2 mL), EtN (0.3 mL), and water (0.1 mL) at 50° C. for 16 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA). The resulting material was filtered through an SCX column to give the title compound (35 mg, 42%). ESI-MS m / z calcd for [C 16 H 15 Cl2N5O4S2] [M+H]+ :500.0;found:500.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.60(s,1H),7.95(s,1H),7.93(s,1H),7.71(s,1H),7.46(s,1H),5.98(d,J=5.2 Hz,1H),5.05(dd,J=11.5,2.7 Hz,1H),4.93(dd,J=11.5,5.4 Hz,1H),4.44(t,J=6.2 Hz,1H),4.23-4.17(m,1H),3.77-3.65(m,2H).

[0213] Example 52 3-Chloro-4-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 3-chloro-4-cyanophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (111 mg, 0.23 mmol), CuI (8.8 mg, 0.046 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (60 mg, 0.28 mmol) in MeCN (2.0 mL) was added EtN (128 μL, 0.92 mmol) and TBAF (23 μL, 1 M in THF, 0.023 mmol), and the mixture was stirred at 50° C. for 90 min. The mixture was filtered and concentrated, and the residue was stirred in MeOH (2 mL), EtN (0.3 mL), and water (0.1 mL) at 50° C. for 20 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1% TFA). The resulting material was filtered through an SCX column to give the title compound (81 mg, 70%). ESI-MS m / z calcd for [C 16 H 15 Cl2N5O4S2] [M+H] + :500.0;found:500.0. 1H NMR(400 MHz,Methanol-d4)δ 8.60(s,1H),7.86(d,J=1.4 Hz,1H),7.71(d,J=8.3 Hz,1H),7.66(dd,J=8.2,1.5 Hz,1H),7.46(s,1H),6.11(d,J=5.3 Hz,1H),5.06(dd,J=11.4,2.8 Hz,1H),4.96(dd,J=11.3,5.5 Hz,1H),4.38(t,J=6.1 Hz,1H),4.23-4.17(m,1H),3.77-3.63(m,2H).

[0214] Example 53 5-Chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloropyridin-3-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (69.4 mg, 0.20 mmol), CuI (7.6 mg, 0.040 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (51.8 mg, 0.24 mmol) in MeCN (2.0 mL) was added EtN (112 μL, 0.80 mmol) and TBAF (20 μL, 1 M in THF, 0.020 mmol), and the mixture was stirred at 50° C. for 90 min. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA) to give the title compound (13 mg, 13%). ESI-MS m / z calculated for [C 17 H 17 Cl2N5O4S2] [M+H] + :490.0;found:490.0. 1H NMR(500 MHz,Methanol-d4)δ 8.68(s,1H),8.66(s,1H),8.50(s,1H),8.24(t,J=2.0 Hz,1H),7.49(s,1H),6.30(d,J=5.3 Hz,1H),5.11(dd,J=11.4,2.9 Hz,1H),4.67(dd,J=11.3,5.3 Hz,1H),4.49(t,J=6.1 Hz,1H),4.22(d,J=2.2 Hz,1H),3.78-3.66(m,2H),3.44(s,3H).

[0215] Example 54 5-Bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (516 mg, 0.99 mmol) in MeCN (40 mL) was added benzaldehyde dimethyl acetal (0.30 mL, 1.98 mmol), followed by p-toluenesulfonic acid monohydrate (94 mg, 0.50 mmol), and the mixture was stirred at rt for 20 h. EtN (0.14 mL, 0.99 mmol) was added, and the mixture was concentrated. The residue was partitioned between EtOAc and saturated aqueous NaHCO. The organic phase was dried and evaporated, and the residue was dissolved in DMF (5 mL) along with NaH (60% in oil, 60 mg, 1.56 mmol). Iodomethane (78 μL, 1.17 mmol) was added and the mixture was stirred at rt for 1 h. The mixture was diluted with EtOAc and washed twice with water, and the organic phase was dried and evaporated. The residue was stirred in TFA / water (5 mL, 4:1) at rt for 30 min. The mixture was concentrated to half its volume and partitioned between EtOAc and aqueous NaOH (1 M). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc). Preparative HPLC (C 18Further purification by HCl / MeCN / 0.1% TFA gave the title compound (191 mg, 46%). ESI-MS m / z calculated for [C 17 H 17 BrClN5O4S2] [M+H] + :534.0;found:534.0. 1 H NMR(500 MHz,Methanol-d4)δ 8.74(s,1H),8.65(s,1H),8.62(s,1H),8.41(t,J=1.9 Hz,1H),7.49(s,1H),6.31(d,J=5.3 Hz,1H),5.11(dd,J=11.3,2.9 Hz,1H),4.67(dd,J=11.3,5.3 Hz,1H),4.48(t,J=6.1 Hz,1H),4.23(d,J=2.3 Hz,1H),3.76-3.68(m,2H),3.44(s,3H).

[0216] Example 55 5-Bromo-2-cyanopyridin-3-yl 3-[4-(4,5-dichlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (75 mg, 0.15 mmol), CuI (7.1 mg, 0.038 mmol), and 4,5-dichloro-2-ethynylthiazole (57 mg, 0.32 mmol) in MeCN (4 mL) was added DIPEA (77 μL, 0.45 mmol), and the mixture was stirred at 50 °C for 16 h. The mixture was concentrated and partitioned between EtOAc and water. The organic phase was dried, evaporated, and purified by chromatography (SiO 2 , PE / EtOAc). The resulting material was stirred in MeOH (2.25 mL), Et 3 N (0.75 mL), and water (0.25 mL) at rt for 3 h. The mixture was concentrated and purified by preparative HPLC (C 18, HO / MeCN / 0.1%TFA) to give the title compound (60 mg, 67%). ESI-MS m / z calcd for [C 18 H 15 BrCl2N6O4S2] [M+H] + :592.9;found:592.9. 1 H NMR(400 MHz,Methanol-d4)δ 8.71(d,J=2.0 Hz,1H),8.67(s,1H),8.62(d,J=2.0 Hz,1H),6.50(d,J=5.3 Hz,1H),5.13(dd,J=11.3,2.9 Hz,1H),4.72(dd,J=11.3,5.3 Hz,1H),4.41(t,J=6.0 Hz,1H),4.20(d,J=2.6 Hz,1H),3.68(d,J=6.0 Hz,2H),3.46(s,3H).

[0217] Example 56 5-Bromo-2-cyanophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanophenyl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (75 mg, 0.18 mmol), CuI (6.9 mg, 0.036 mmol), and trimethyl(2-thiazol-2-ylethynyl)silane (98 mg, 0.27 mmol) in MeCN (2.0 mL) was added EtN (101 μL, 0.72 mmol) and TBAF (18 μL, 1 M in THF, 0.018 mmol), and the mixture was stirred at 50° C. for 5 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18 , H2O / MeCN / 0.1%TFA). The resulting material was further purified by chromatography (SiO2, PE / EtOAc) to give the title compound (30 mg, 32%). ESI-MS m / z calcd for [C 19 H 18BrNOS2] [M+H] + :524.0;found:524.0. 1 H NMR(500 MHz,Methanol-d4)δ 8.64(s,1H),8.18(d,J=1.5 Hz,1H),7.92(d,J=3.3 Hz,1H),7.73-7.68(m,2H),7.67(d,J=3.3 Hz,1H),6.42(d,J=5.4 Hz,1H),5.14(dd,J=11.3,2.9 Hz,1H),4.71(dd,J=11.3,5.3 Hz,1H),4.47(t,J=6.1 Hz,1H),4.26(d,J=2.8 Hz,1H),3.73(dd,J=11.5,5.5 Hz,1H),3.67(dd,J=11.5,6.7 Hz,1H),3.49(s,3H).

[0218] Example 57 5-Bromo-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanophenyl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (75 mg, 0.18 mmol), CuI (6.9 mg, 0.036 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (59 mg, 0.27 mmol) in MeCN (2.0 mL) was added EtN (101 μL, 0.72 mmol) and TBAF (18 μL, 1 M in THF, 0.018 mmol), and the mixture was stirred at 50° C. for 4 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA) to give the title compound (71 mg, 70%). ESI-MS m / z calcd for [C 19 H 17 BrClN5O4S2] [M+H] + :558.0;found:558.0. 1H NMR(500 MHz,Methanol-d4)δ 8.66(s,1H),8.17(s,1H),7.73-7.66(m,2H),7.49(s,1H),6.42(d,J=5.3 Hz,1H),5.13(dd,J=11.3,2.9 Hz,1H),4.72(dd,J=11.3,5.3 Hz,1H),4.47(t,J=6.1 Hz,1H),4.25(d,J=2.7 Hz,1H),3.73(dd,J=11.5,5.5 Hz,1H),3.67(dd,J=11.4,6.7 Hz,1H),3.49(s,3H).

[0219] Example 58 5-Bromo-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanophenyl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (75 mg, 0.18 mmol), CuI (6.9 mg, 0.036 mmol), and 4-(2-trimethylsilylethynyl)thiazol-2-ol (54 mg, 0.27 mmol) in MeCN (2.0 mL) was added EtN (101 μL, 0.72 mmol) and TBAF (18 μL, 1 M in THF, 0.018 mmol), and the mixture was stirred at 50° C. for 4 h. Additional 4-(2-trimethylsilylethynyl)thiazol-2-ol (54 mg, 0.27 mmol) was added, and the mixture was stirred at 50° C. for an additional 2 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (45 mg, 46%). ESI-MS m / z calcd for [C 19 H 18 BrN5O5S2] [M+H] + :540.0;found:540.0. 1H NMR(500 MHz,Methanol-d4)δ 8.39(s,1H),8.17(d,J=1.0 Hz,1H),7.73-7.66(m,2H),6.73(s,1H),6.41(d,J=5.3 Hz,1H),5.08(dd,J=11.3,2.9 Hz,1H),4.63(dd,J=11.3,5.3 Hz,1H),4.45(t,J=6.0 Hz,1H),4.23(d,J=2.3 Hz,1H),3.72(dd,J=11.4,5.5 Hz,1H),3.66(dd,J=11.4,6.7 Hz,1H),3.47(s,3H).

[0220] Example 59 5-Bromo-2-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanophenyl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (75 mg, 0.18 mmol), CuI (6.9 mg, 0.036 mmol), and 4-(2-trimethylsilylethynyl)thiazol-2-amine (53 mg, 0.27 mmol) in MeCN (2.0 mL) was added EtN (101 μL, 0.72 mmol) and TBAF (18 μL, 1 M in THF, 0.018 mmol), and the mixture was stirred at 50° C. for 5 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA) to give the title compound (63 mg, 65%). ESI-MS m / z calcd for [C 19 H 19 BrN6O4S2] [M+H] + :539.0;found:539.0. 1H NMR(500 MHz,Methanol-d4)δ 8.79-8.37(m,1H),8.20-8.11(m,1H),7.75-7.66(m,2H),7.37-6.93(m,1H ),6.49-6.40(m,1H),5.26-5.06(m,1H),4.75-4.62(m,1H),4.47(t,J=5.9 Hz,1H),4.37-4.19(m,1H),3.73(dd,J=11.4,5.4 Hz,1H),3.68(dd,J=11.4,6.6 Hz,1H),3.48(s,3H).

[0221] Example 60 5-Bromo-2-(N-methylcarbonyl)phenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-(N-methylcarbonyl)phenyl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (100 mg, 0.20 mmol), CuI (8.5 mg, 0.045 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (60 mg, 0.28 mmol) in MeCN (2.5 mL) was added DIPEA (0.12 mL, 0.67 mmol), and the mixture was stirred at 50 °C for 3 h. The mixture was analyzed by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (89 mg, 67%). ESI-MS m / z calcd for [C 20 H 21 BrClN5O5S2] [M+H] + :590.0;found:590.0. 1H NMR(500 MHz,Methanol-d4)δ 8.61(s,1H),8.00(d,J=1.9 Hz,1H),7.56(dd,J=8.2,1.9 Hz,1H),7.46(s,1H),7.32(d,J=8.2 Hz,1H),6.18(d,J=5.3 Hz,1H),5.05(dd,J=11.4,2.9 Hz,1H),4.60(dd,J=11.4,5.4 Hz,1H),4.49(t,J=6.4 Hz,1H),4.20(d,J=2.1 Hz,1H),3.73(dd,J=11.4,5.6 Hz,1H),3.69(dd,J=11.4,6.7 Hz,1H),3.40(s,3H),2.91(s,3H).

[0222] Example 61 5-Bromo-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-(N-methyl-carbonyl)phenyl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (85.0 mg, 0.13 mmol) in DCM (5 mL), TFA (0.3 mL) was added at 0 °C, and the mixture was stirred at rt overnight. EtN (0.5 mL) was added at 0 °C, and the mixture was concentrated. The residue was purified by preparative HPLC [MeCN / H O (10 mmol / L NH HCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (60.7 mg, 83%). ESI-MS m / z calcd for [C 20 H 22 BrN5O5S2] [M+H] + :556.0;found:556.0. 1H NMR(400 MHz,Methanol-d4)δ 8.61(s,1H),8.03(d,J=2.0 Hz,1H),7.91(d,J=3.2 Hz,1H),7.66(d,J=3.2 Hz,1H),7.58(dd,J=8.0,2.0 Hz,1H),7.34(d,J=8.0 Hz,1H),6.20(d,J=5.2 Hz,1H),5.08(dd,J=11.2,2.8 Hz,1H),4.62(dd,J=11.2,5.2 Hz,1H),4.51(t,J=6.0 Hz,1H),4.25-4.20(m,1H),3.79-3.66(m,2H),3.41(s,3H),2.93(s,3H).

[0223] Example 62 5-Chloro-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(N-methyl-carbonyl)phenyl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (120 mg, 0.20 mmol) in DCM (5 mL), TFA (0.3 mL) was added at 0 °C, and the mixture was stirred at rt overnight. EtN (0.5 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (60 mg, 59%). ESI-MS m / z calcd for [C 20 H 22 ClN5O5S2] [M+H] + :512.1;found:512.0. 1H NMR(400 MHz,Methanol-d4)δ 8.59(m,1H),7.95-7.84(m,2H),7.64(d,J=3.2 Hz,1H),7.39(d,J=2.8 Hz,2H),6.20(t,J=4.0 Hz,1H),5.06(d,J=11.2 Hz,1H),4.66-4.57(m,1H),4.54-4.45(m,1H),4.20(s,1H),3.78-3.66(m,2H),3.40(s,3H),2.92(m,3H).

[0224] Example 63 5-Bromo-2-cyanophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (90 mg, 0.14 mmol) in DCM (5 mL) was added TFA (0.32 mL) at 0 °C, and the mixture was stirred at rt overnight. EtN (0.5 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H O (10 mmol / L NH HCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (40.1 mg, 52%). ESI-MS m / z calcd for [C 20 H 20 BrNOS2] [M+H] + :538.0;found:538.0. 1H NMR(400 MHz,Methanol-d4)δ 8.61(s,1H),8.20-8.15(m,1H),7.74-7.65(m,2H),7.23-7.18(m,1H),6.42(d,J=5.2 Hz,1H),5.17-5.09(m,1H),4.74-4.65(m,1H),4.49-4.45(m,1H),4.28-4.23(m,1H),3.77-3.62(m,2H),3.49(s,3H),2.52-2.48(m,3H).

[0225] Example 64 5-Bromo-2-cyanopyridin-3-yl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (100 mg, 0.17 mmol) in DCM / TFA (10 mL, 19:1) was stirred overnight at rt. EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (52.5 mg, 55%). ESI-MS m / z calcd for [C 19 H 18 BrClN6O4S2] [M+H] + :573.0;found:573.0. 1H NMR(400 MHz,Methanol-d4)δ 8.71(d,J=2.0 Hz,1H),8.62(d,J=2.0 Hz,1H),8.59(s,1H),6.50(d,J=5.2 Hz,1H),5.12(dd,J=11.2,2.8 Hz,1H),4.70(dd,J=11.2,5.2 Hz,1H),4.40(t,J=6.0 Hz,1H),4.20(d,J=2.4 Hz,1H),3.68(d,J=6.0 Hz,2H),3.46(s,3H),2.41(s,3H).

[0226] Example 65 5-Bromo-2-cyanophenyl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanophenyl 4,6-O-benzylidene-3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (95 mg, 0.14 mmol) in DCM (5 mL) was added TFA (0.32 mL) at 0 °C, and the mixture was stirred at rt overnight. EtN (0.5 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H O (10 mmol / L NH HCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (32 mg, 39%). ESI-MS m / z calcd for [C 20 H 19 BrClN5O4S2] [M+H] + :572.0;found:572.0. 1H NMR(400 MHz,Methanol-d4)δ 8.61(s,1H),8.20-8.15(m,1H),7.74-7.65(m,2H),6.42(d,J=5.2 Hz,1H),5.12(dd,J=11.2,2.8 Hz,1H),4.69(dd,J=11.2,5.2 Hz,1H),4.46(t,J=6.0 Hz,1H),4.26-4.21(m,1H),3.76-3.62(m,2H),3.48(s,3H),2.43(s,3H).

[0227] Example 66 2,5-Dichlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 2,5-dichlorophenyl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (120 mg, 0.21 mmol) in DCM (5 mL) was added TFA (0.4 mL) at 0 °C, and the mixture was stirred at rt overnight. EtN (0.5 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (72 mg, 71%). ESI-MS m / z calcd for [C 18 H 18 Cl2N4O4S2] [M+H] + :489.0;found:489.0. 1H NMR(400 MHz,Methanol-d4)δ 8.86(s,1H),8.14(d,J=3.2 Hz,1H),8.09(d,J=2.4 Hz,1H),7.89(d,J=3.2 Hz,1H),7.70(d,J=8.4 Hz,1H),7.54(dd,J=8.4,2.4 Hz,1H),6.57(d,J=5.2 Hz,1H),5.36(dd,J=11.2,2.8 Hz,1H),4.92(dd,J=11.2,5.2 Hz,1H),4.67(t,J=6.0 Hz,1H),4.50-4.45(m,1H),4.00-3.91(m,1H),3.91-3.83(m,1H),3.68(s,3H).

[0228] Example 67 5-Bromo-2-chlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-chlorophenyl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (180 mg, 0.29 mmol) in DCM (15 mL), TFA (0.75 mL) was added, and the mixture was stirred at rt overnight. EtN (1.5 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H O (10 mmol / L NH HCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (75 mg, 49%). ESI-MS m / z calcd for [C 18 H 18 BrClN4O4S2] [M+H] + :535.0;found:535.0. 1H NMR(400 MHz,Methanol-d4)δ 8.61(s,1H),7.98(d,J=2.0 Hz,1H),7.89(d,J=3.2 Hz,1H),7.64(d,J=3.2 Hz,1H),7.45-7.37(m,2H),6.31(d,J=5.2 Hz,1H),5.11(dd,J=11.2,3.2 Hz,1H),4.67(dd,J=11.2,5.2 Hz,1H),4.43(t,J=6.4 Hz,1H),4.23(d,J=2.4 Hz,1H),3.73-3.60(m,2H),3.31(s,3H).

[0229] Example 68 5-Chloro-2-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-fluorophenyl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (180 mg, 0.32 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt overnight. EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (76.7 mg, 51%). ESI-MS m / z calcd for [C 18 H 18 ClFN4O4S2] [M+H] + :473.0;found:473.2. 1H NMR(400 MHz,Methanol-d4)δ 8.61(s,1H),7.89(d,J=3.2 Hz,1H),7.76(dd,J=6.4,2.8 Hz,1H),7.64(d,J=3.2 Hz,1H),7.41-7.32(m,1H),7.18(t,J=8.8 Hz,1H),6.23(d,J=5.8 Hz,1H),5.11(dd,J=11.2,2.8 Hz,1H),4.64(dd,J=11.2,5.2 Hz,1H),4.48-4.40(m,1H),4.25-4.20(m,1H),3.68(dd,J=11.2,6.0 Hz,1H),3.58(dd,J=11.2,6.0 Hz,1H),3.43(s,3H).

[0230] Example 69 5-Bromo-2-fluorophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-fluorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (110 mg, 0.18 mmol) in DCM (5 mL), TFA (0.40 mL) was added, and the mixture was stirred at rt overnight. EtN (0.5 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H O (10 mmol / L NH HCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (63.4 mg, 67%). ESI-MS m / z calcd for [C 19 H 20 BrFN4O4S2] [M+H] + :531.0;found:531.0. 1H NMR(400 MHz,Methanol-d4)δ 8.60(s,1H),7.91(dd,J=6.4,2.4 Hz,1H),7.57-7.49(m,1H),7.23-7.18(m,1H),7.14(t,J=8.8 Hz,1H),6.23(d,J=5.2 Hz,1H),5.12(dd,J=11.2,2.8 Hz,1H),4.64(dd,J=11.2,5.2 Hz,1H),4.50-4.42(m,1H),4.27-4.22(m,1H),3.75-3.66(m,1H),3.64-3.56(m,1H),3.45(s,3H),2.52-2.47(m,3H).

[0231] Example 70 5-Chloro-2-cyanopyridin-3-yl 3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanopyridin-3-yl 2,4,6-tri-O-acetyl-3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (90 mg, 0.14 mmol) in MeOH (5 mL), EtN (3 mL), and water (1 mL) was stirred overnight at rt. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (47.9 mg, 67%). ESI-MS m / z calculation for [C 17 H 14 Cl2N6O4S2] [M+H] + :501.0;found:501.0. 1H NMR(400 MHz,Methanol-d4)δ 8.46(d,J=2.0 Hz,1H),8.35(d,J=2.0 Hz,1H),8.33(s,1H),7.77(s,1H),6.13(d,J=5.0 Hz,1H),5.00(dd,J=11.2,2.8 Hz,1H),4.90(dd,J=11.2,5.2 Hz,1H),4.27(t,J=6.0 Hz,1H),4.12(d,J=2.0 Hz,1H),3.57(d,J=6.0 Hz,2H).

[0232] Example 71 5-Chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-ethyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-deoxy-2-O-ethyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (85 mg, 0.15 mmol) in DCM (10 mL), TFA (0.54 mL) was added and the mixture was stirred at rt for 6 h. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (45 mg, 62%). ESI-MS m / z calcd for [C 19 H 19 ClN6O4S2] [M+H] + :495.1;found:495.2. 1H NMR(400 MHz,Methanol-d4)δ 8.60(d,J=2.4 Hz,1H),8.59(s,1H),8.46(d,J=2.4 Hz,1H),7.89(d,J=3.2 Hz,1H),7.64(d,J=3.6 Hz,1H),6.48(d,J=5.2 Hz,1H),5.13(dd,J=11.2,2.8 Hz,1H),4.79(dd,J=11.2,5.2 Hz,1H),4.39(t,J=6.0 Hz,1H),4.21(d,J=2.4 Hz,1H),3.91-3.84(m,1H),3.67(t,J=6.0 Hz,2H),3.51-3.44(m,1H),1.07-1.03(m,3H).

[0233] Example 72 5-Chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-{4-[2-(di-tert-butoxycarbonylamino)thiazol-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (180 mg, 0.21 mmol) in DCM (16 mL) was added TFA (0.79 mL), and the mixture was stirred at rt for 6 h. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (26.5 mg, 56%). ESI-MS m / z calcd for [C 19 H 20 ClN7O4S2] [M+H] + :510.1;found:510.2. 1H NMR(400 MHz,Methanol-d4)δ 8.59(d,J=2.0 Hz,1H),8.46(d,J=2.0 Hz,1H),8.25(s,1H),6.96(s,1H),6.46(d,J=5.2 Hz,1H),5.05(dd,J=11.2,2.8 Hz,1H),4.73(dd,J=11.6,5.6 Hz,1H),4.37(t,J=6.0 Hz,1H),4.19(d,J=2.4 Hz,1H),3.89-3.82(m,1H),3.66(d,J=6.0 Hz,2H),3.48-3.42(m,1H),1.06-1.03(m,3H).

[0234] Example 73 5-Chloro-2-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (62 mg, 0.11 mmol) in DCM (4 mL), TFA (0.40 mL) was added, and the mixture was stirred at rt for 2 h. EtN (1 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (17 mg, 32%). ESI-MS m / z calcd for [C 19 H 19 ClN6O4S2] [M+H] + :495.1;found:495.2. 1H NMR(400 MHz,Methanol-d4)δ 8.25(s,1H),7.99(d,J=2.0 Hz,1H),7.75(d,J=4.4 Hz,1H),7.49(dd,J=8.4,2.0 Hz,1H),6.96(s,1H),6.39(d,J=5.2 Hz,1H),5.03(dd,J=11.2,2.8 Hz,1H),4.62(dd,J=11.2,5.2 Hz,1H),4.42(t,J=6.0 Hz,1H),4.20(d,J=2.4 Hz,1H),3.71-3.61(m,2H),3.44(s,3H).

[0235] Example 74 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 2,4,6-tri-O-acetyl-3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (15 mg, 0.023 mmol) in MeOH (5 mL) was stirred overnight at room temperature with EtN (1 mL) and water (0.5 mL). The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (5.4 mg, 45%). ESI-MS m / z calculation for [C 19 H 19 ClN8O4S2] [M+H] + :523.1;found:523.2. 1H NMR(400 MHz,DMSO-d6)δ 12.85-12.73(m,1H),8.45(d,J=2.0 Hz,1H),8.28(d,J=2.0 Hz,1H),8.07(s,1H),7.28(s,1H),7.20(s,1H),7.07(s,2H),6.91(s,1H),6.02(d,J=5.2 Hz,1H),5.93(d,J=5.2 Hz,1H),5.47(d,J=6.8 Hz,1H),4.93-4.85(m,1H),4.83-4.73(m,1H),4.64(t,J=5.6 Hz,1H),4.15(t,J=6.4 Hz,1H),4.03-3.97(m,1H),3.60-3.50(m,1H),3.45-3.35(m,1H).

[0236] Example 75 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside (80 mg, 0.20 mmol) in DMF (4 mL) was added 4-(2-trimethylsilylethynyl)thiazol-2-ol (39.6 mg, 0.20 mmol), copper(II) sulfate pentahydrate (50.1 mg, 0.20 mmol), sodium (+)-L-ascorbate (39.7 mg, 0.20 mmol), CsF (30.5 mg, 0.20 mmol), and N,N,N',N'-tetramethylethylenediamine (60 μL, 0.40 mmol), and the mixture was stirred at rt for 72 h. The mixture was filtered, and the filtrate was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (1.65 mg, 2%). ESI-MS m / z calcd for [C 19 H18 ClN7O5S2] [M+H] + :524.0;found:524.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.47-8.42(m,1H),8.35(s,1H),8.31(d,J=2.0 Hz,1H),7.25-7.21(m,2H),6.69(s,1H),6.00(d,J=5.6 Hz,1H),5.15-5.07(m,1H),4.93-4.88(m,1H),4.41-4.34(m,1H),4.19-4.15(m,1H),3.77-3.62(m,2H).

[0237] Example 76 5-Chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (36 mg, 0.055 mmol) in DCM / TFA (4 mL, 19:1) was stirred at rt for 6 h. EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (9.1 mg, 29%). ESI-MS m / z calcd for [C 22 H 20 Cl2N6O4S2] [M+H] + :567.0;found:567.0. 1H NMR(400 MHz,Methanol-d4)δ 8.68-8.66(m,1H),8.56(s,1H),8.51(d,J=2.0 Hz,1H),8.44(d,J=2.4 Hz,1H),8.00-7.96(m,1H),7.85-7.83(m,1H),7.51-7.48(m,1H),7.44(s,1H),6.19(d,J=5.2 Hz,1H),4.98-4.92(m,1H),4.59(dd,J=11.6,5.2 Hz,1H),4.28(t,J=6.0 Hz,1H),4.11(d,J=2.0 Hz,1H),3.70-3.62(m,2H),3.18(s,3H).

[0238] Example 77 2-Cyano-5-methylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2-cyano-5-methylpyridin-3-yl 2,4,6-tri-O-acetyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (55 mg, 0.091 mmol) in MeOH (10 mL), EtN (0.8 mL), and water (0.5 mL) was stirred overnight at rt. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (36 mg, 83%). ESI-MS m / z calculation for [C 18 H 17 ClN6O4S2] [M+H] + :481.0;found:481.0. 1H NMR(400 MHz,DMSO-d6)δ 8.72(s,1H),8.49-8.44(m,1H),8.23-8.18(m,1H),7.79(s,1H),6.13(dd,J=17.2,4.4 Hz,2H),5.50(d,J=6.8 Hz,1H),5.00-4.87(m,2H),4.70(t,J=5.6 Hz,1H),4.21-4.16(m,1H),4.11-4.04(m,1H),3.55-3.45(m,1H),3.42-3.33(m,1H),2.39(s,3H).

[0239] Example 78 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-azido-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside (38 mg, 0.085 mmol) in DMF (2 mL) was added 4-(2-trimethylsilylethynyl)thiazol-2-amine (25 mg, 0.13 mmol), copper(II) sulfate pentahydrate (10.6 mg, 0.042 mmol), and sodium (+)-L-ascorbate (8 mg, 0.042 mmol), and the mixture was stirred at rt for 4 h. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (11.4 mg, 24%). ESI-MS m / z calculation for [C 19 H 18 Cl2F3N5O4S2] [M+H] + :572.0;found:572.1. 1H NMR(400 MHz,Methanol-d4)δ 8.28(s,1H),7.82(d,J=2.0 Hz,1H),7.55-7.48(m,2H),8.95(s,1H),6.13(d,J=4.8 Hz,1H),5.08-5.03(m,2H),4.49(t,J=6.0 Hz,1H),4.19-4.12(m,2H),3.97-3.92(m,1H),3.73-3.64(m,2H).

[0240] Example 79 3,4-Dichlorophenyl 3-deoxy-2-O-(2,2,2-trifluoroethyl)-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-azido-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside (38 mg, 0.085 mmol) in DMF (2 mL) was added 4-(2-trimethylsilylethynyl)thiazol-2-amine (25 mg, 0.13 mmol), copper(II) sulfate pentahydrate (10.6 mg, 0.042 mmol), and sodium (+)-L-ascorbate (8 mg, 0.042 mmol), and the mixture was stirred at rt for 4 h. The mixture was concentrated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (8.9 mg, 18%). ESI-MS m / z calculation for [C 19 H 17 Cl2F3N4O5S2] [M+H] + :573.0;found:573.0. 1H NMR(400 MHz,Methanol-d4)δ 8.28(s,1H),7.82(s,1H),7.55-7.48(m,2H),6.67(s,1H),6.13(d,J=4.4 Hz,1H),5.10-4.98(m,2H),4.46(t,J=4.0 Hz,1H),4.20-4.12(m,2H),3.97-3.93(m,1H),3.73-3.65(m,2H).

[0241] Example 80 5-Ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 2,4,6-tri-O-acetyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (100 mg, 0.15 mmol) in MeOH (5 mL) was added KF (13.1 mg, 0.23 mmol), and the mixture was stirred at room temperature for 30 min. EtN (1.05 mL, 7.53 mmol) and water (0.5 mL) were added, and the mixture was stirred at room temperature overnight. The mixture was concentrated and purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (42 mg, 60%). ESI-MS m / z calcd for [C 18 H 16 ClN5O4S2] [M+H] + :466.0;found:466.2. 1H NMR(400 MHz,Methanol-d4)δ 8.68(d,J=2.0 Hz,1H),8.59(s,1H),8.52(d,J=2.0 Hz,1H),8.16(t,J=2.0 Hz,1H),7.46(s,1H),5.88(d,J=5.2 Hz,1H),5.10-5.02(m,1H),4.96-4.87(m,1H),4.48(t,J=6.4 Hz,1H),4.24-4.18(m,1H),3.84(s,1H),3.76-3.62(m,2H).

[0242] Example 81 5-Ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 4,6-O-benzylidene-3-{4-[2-(di-tert-butoxycarbonylamino)thiazol-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (110 mg, 0.13 mmol) in DCM (6 mL) was added TFA (1.0 mL) and the mixture was stirred at rt overnight. EtN (2 mL) was added at 0 °C to neutralize the TFA. The mixture was evaporated, and the residue was dissolved in DMF (3 mL). KF (15.6 mg, 0.27 mmol) was added, and the mixture was stirred at rt for 1 h. The mixture was filtered, and the filtrate was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (45 mg, 73%). ESI-MS m / z calcd for [C 19 H 20 N6O4S2] [M+H] + :461.1;found:461.2. 1H NMR(400 MHz,Methanol-d4)δ 8.70(d,J=2.0 Hz,1H),8.53(d,J=2.0 Hz,1H),8.24(s,1H),8.19(t,J=2.0 Hz,1H),6.95(s,1H),6.23(d,J=5.2 Hz,1H),5.01(dd,J=11.2,2.8 Hz,1H),4.57(dd,J=11.2,5.2 Hz,1H),4.45(dd,J=7.2,5.6 Hz,1H),4.18(dd,J=2.8,1.2 Hz,1H),3.74-3.60(m,2H),3.39(s,3H).

[0243] Example 82 5-Cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-cyanopyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (90 mg, 0.16 mmol) in DCM (4 mL), TFA (0.25 mL) was added, and the mixture was stirred at rt overnight. EtN (0.5 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H O (10 mmol / L NH HCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (48 mg, 63%). ESI-MS m / z calcd for [C 18 H 17 ClN6O4S2] [M+H] + :481.0;found:481.0. 1H NMR(400 MHz,Methanol-d4)δ 8.95(d,J=2.0 Hz,1H),8.80(d,J=2.0 Hz,1H),8.63(s,1H),8.50(t,J=2.0 Hz,1H),7.46(s,1H),6.35(d,J=5.2 Hz,1H),5.10(dd,J=11.2,2.8 Hz,1H),4.70-4.61(m,1H),4.43(t,J=6.0 Hz,1H),4.21-4.16(m,1H),3.68(d,J=6.0 Hz,2H),3.41(s,3H).

[0244] Example 83 5-Cyanopyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-cyanopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (50 mg, 0.091 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 3 h, after which EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (15.8 mg, 38%). ESI-MS m / z calcd for [C 18 H 18 N6O5S2] [M+H] + :463.1;found:463.0. 1H NMR(400 MHz,Methanol-d4)δ 8.95(d,J=2.0 Hz,1H),8.79(d,J=2.0 Hz,1H),8.49(t,J=2.0 Hz,1H),8.31(s,1H),6.68(s,1H),6.33(d,J=5.2 Hz,1H),5.03(dd,J=11.2,2.8 Hz,1H),4.58(dd,J=11.2,5.2 Hz,1H),4.42(t,J=6.0 Hz,1H),4.16(d,J=3.6 Hz,1H),3.68(d,J=6.0 Hz,2H),3.39(s,3H).

[0245] Example 84 2-Cyano-5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2-cyano-5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 2,4,6-tri-O-acetyl-3-{4-[2-(di-tert-butoxycarbonylamino)thiazol-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-1-thio-α-D-galactopyranoside (100 mg, 0.12 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 1 h. The reaction was neutralized with EtN, concentrated, and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254]. The resulting material was stirred in MeOH (5 mL) and catalytic NaOMe for 15 min at rt. The mixture was neutralized with acidic resin, filtered, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (19.6 mg, 51%). ESI-MS m / z calcd for [C 19 H 17 N7O4S2] [M+H]+ :472.1;found:472.2. 1 H NMR(400 MHz,Methanol-d4)δ 8.60(d,J=2.0 Hz,1H),8.40(d,J=2.0 Hz,1H),8.24(s,1H),6.95(s,1H),6.18(d,J=5.2 Hz,1H),5.05(dd,J=11.2,2.8 Hz,1H),4.94(dd,J=11.2,5.2 Hz,1H),4.35(dd,J=6.8,5.2 Hz,1H),4.20(dd,J=2.8,1.2 Hz,1H),3.71-3.58(m,2H).

[0246] Example 85 2-Cyano-5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 2-cyano-5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 4,6-O-benzylidene-3-{4-[2-(di-tert-butoxycarbonylamino)thiazol-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (110 mg, 0.13 mmol) in DCM (6 mL) was added TFA (0.97 mL), and the mixture was stirred at rt overnight. EtN (2 mL) was added at 0 °C to neutralize the TFA. The mixture was concentrated, and the residue was dissolved in DMF (3 mL) along with KF (15.6 mg, 0.27 mmol). The mixture was stirred at rt for 1 h, then filtered and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (27 mg, 43%). ESI-MS m / z calcd for [C 20 H 19 N7O4S2] [M+H] + :486.1;found:486.2.1 H NMR(400 MHz,Methanol-d4)δ 8.64(d,J=2.0 Hz,1H),8.43(d,J=2.0 Hz,1H),8.25(s,1H),6.96(s,1H),6.47(d,J=5.2 Hz,1H),5.06(dd,J=11.2,2.8 Hz,1H),4.64(dd,J=11.2,5.2 Hz,1H),4.39(t,J=6.0 Hz,1H),4.22-4.16(m,1H),3.72-3.59(m,2H),3.44(s,3H).

[0247] Example 86 5-Bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (85 mg, 0.13 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt for 1 h, after which EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (45.4 mg, 62%). ESI-MS m / z calcd for [C 19 H 18 BrClN6O4S2] [M+H] + :573.0;found:573.0. 1H NMR(400 MHz,Methanol-d4)δ 8.70(d,J=2.0 Hz,1H),8.64(s,1H),8.61(d,J=2.0 Hz,1H),7.46(s,1H),6.46(d,J=5.2 Hz,1H),5.12(dd,J=11.2,2.8 Hz,1H),4.80(dd,J=11.2,5.2 Hz,1H),4.40(t,J=6.0 Hz,1H),4.21(dd,J=2.8,1.2 Hz,1H),3.92-3.80(m,1H),3.68(d,J=6.0 Hz,2H),3.52-3.39(m,1H),1.05(t,J=6.8 Hz,3H).

[0248] Example 87 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside [ka] A solution of 3,4-dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzylidene-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (130 mg, 0.16 mmol) in DCM / TFA (10 mL, 19:1) was stirred overnight at rt, after which EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (49 mg, 59%). ESI-MS m / z calculation for [C 19 H 21 Cl2N5O4S2] [M+H] + :518.0;found:518.2. 1H NMR(400 MHz,Methanol-d4)δ 8.23(s,1H),7.79(d,J=2.0 Hz,1H),7.52(dd,J=8.4,2.0 Hz,1H),7.47(d,J=8.4 Hz,1H),6.95(s,1H),6.13(d,J=5.2 Hz,1H),4.98(dd,J=11.2,2.8 Hz,1H),4.64(dd,J=11.2,5.2 Hz,1H),4.43(t,J=6.4 Hz,1H),4.18(dd,J=2.8,1.2 Hz,1H),3.84-3.55(m,3H),3.46-3.35(m,1H),1.01(t,J=6.8 Hz,3H).

[0249] Example 88 3-Chloro-4-cyanophenyl 4,6-O-benzylidene-3-{4-[2-(di-tert-butoxycarbonylamino)thiazol-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside [ka] A solution of 3-chloro-4-cyanophenyl 4,6-O-benzylidene-3-{4-[2-(di-tert-butoxycarbonylamino)thiazol-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (90 mg, 0.11 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt overnight, after which EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (30 mg, 47%). ESI-MS m / z calcd for [C 20 H 21 ClN6O4S2] [M+H] + :509.1;found:509.0. 1H NMR(400 MHz,Methanol-d4)δ 8.24(s,1H),7.86(d,J=1.6 Hz,1H),7.70(d,J=8.4 Hz,1H),7.65(dd,J=8.4,1.6 Hz,1H),6.95(s,1H),6.43(d,J=5.2 Hz,1H),5.01(dd,J=11.2,2.8 Hz,1H),4.69(dd,J=11.2,5.2 Hz,1H),4.32(t,J=6.0 Hz,1H),4.17(dd,J=2.8,1.2 Hz,1H),3.83-3.59(m,3H),3.46-3.35(m,1H),0.99(t,J=6.8 Hz,3H).

[0250] Example 89 3-Chloro-4-cyanophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 4,6-di-O-acetyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-D-galactal (880 mg, 2.31 mmol) and oxotrichloro[(dimethylsulfide)triphenylphosphine oxide]rhenium(V) (150 mg, 0.23 mmol) in toluene (20 mL) was added 2-chloro-4-sulfanylbenzonitrile (589 mg, 3.47 mmol), and the mixture was stirred at 70 °C for 20 h. The mixture was evaporated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254]. The resulting material was stirred in MeOH (5 mL) and catalytic NaOMe at rt for 1 h. The mixture was neutralized with acidic resin, filtered, concentrated, and purified by prep-SFC to give the title compound (13.5 mg, 1%). ESI-MS m / z calcd for [C 18 H 16 ClN5O4S2] [M+H] +:466.0;found:466.0, 1 H NMR(400 MHz,Methanol-d4)δ 8.28(s,1H),7.84(d,J=1.6 Hz,1H),7.71-7.62(m,2H),6.67(s,1H),6.18(d,J=5.2 Hz,1H),5.19-5.14(m,1H),4.37(t,J=6.0 Hz,1H),4.21(dd,J=5.2,2.0 Hz,1H),4.15(s,1H),3.73-3.71(m,1H),3.17-3.09(m,1H),2.33(dd,J=13.6,4.4 Hz,1H).

[0251] Example 90 5-Bromo-2-(N,N-dimethylcarbamoyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-carboxypyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (30 mg, 0.051 mmol) in DMF (2 mL) was added dimethylamine hydrochloride (16.5 mg, 0.20 mmol), HATU (96.2 mg, 0.25 mmol), and DIPEA (87 μL, 0.51 mmol), and the mixture was stirred at rt overnight. The mixture was filtered and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (10 mg, 32%). ESI-MS m / z calculation for [C 21 H 24 BrClN6O5S2] [M+H] + :619.0;found:619.0. 1H NMR(400 MHz,Methanol-d4)δ 8.63(d,J=2.0 Hz,1H),8.61(s,1H),8.50(d,J=2.0 Hz,1H),7.46(s,1H),6.25(d,J=5.2 Hz,1H),5.04(dd,J=11.2,2.8 Hz,1H),4.70(dd,J=11.2,5.2 Hz,1H),4.49(t,J=6.0 Hz,1H),4.18(d,J=2.8 Hz,1H),3.85-3.68(m,3H),3.47-3.35(m,1H),3.13(s,3H),2.88(s,3H),1.02(t,J=7.2 Hz,3H).

[0252] Example 91 5-Ethynyl-2-(N,N-dimethylcarbamoyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-ethynyl-2-(N,N-dimethylcarbamoyl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (30 mg, 0.047 mmol) in DCM (5 mL), TFA (0.3 mL) was added, and the mixture was stirred at rt overnight. EtN was added at 0 °C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H O (10 mmol / L NH HCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (15 mg, 58%). ESI-MS m / z calcd for [C 22 H 23 ClN6O5S2] [M+H] + :551.1;found:551.2. 1H NMR(400 MHz,Methanol-d4)δ 8.65-8.59(m,2H),8.38-8.33(m,1H),7.47(s,1H),6.28(d,J=5.2 Hz,1H),5.08-5.01(m,1H),4.66-4.57(m,1H),4.54-4.46(m,1H),4.19(s,1H),3.92(s,1H),3.70(d,J=6.0 Hz,2H),3.39(s,3H),3.15(s,3H),2.88(s,3H).

[0253] Example 92 2-(N-Azetidinylcarbamoyl)-5-ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 2-(N-azetidinylcarbamoyl)-5-ethynylpyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (30 mg, 0.046 mmol) in DCM (5 mL), TFA (0.3 mL) was added, and the mixture was stirred at rt overnight. EtN was added at 0°C to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (5 mg, 19%). ESI-MS m / z calcd for [C 23 H 23 ClN6O5S2] [M+H] + :563.1;found:563.2. 1H NMR(400 MHz,Methanol-d4)δ 8.63(s,1H),8.55(d,J=1.6 Hz,1H),8.36(d,J=1.6 Hz,1H),7.47(s,1H),6.34(d,J=5.2 Hz,1H),5.11(dd,J=11.2,3.2 Hz,1H),4.64(dd,J=11.2,5.2 Hz,1H),4.45(t,J=6.0 Hz,1H),4.28-4.13(m,5H),3.93(s,1H),3.75-3.61(m,2H),3.41(s,3H),2.45-2.33(m,2H).

[0254] Example 93 5-Chloro-2-(N-methylcarbamoyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(N-methylcarbamoyl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (40 mg, 0.063 mmol) in DCM / TFA (10 mL, 19:1) was stirred at rt overnight, after which EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (13.5 mg, 39%). ESI-MS m / z calculation for [C 19 H 20 Cl2N6O5S2] [M+H] + :547.0;found:547.1. 1H NMR(400 MHz,Methanol-d4)δ 8.53(s,1H),8.30(s,2H),7.37(s,1H),6.31(d,J=5.6 Hz,1H),5.08(dd,J=11.6,3.2 Hz,1H),4.59(dd,J=11.6,5.6 Hz,1H),4.27(dd,J=6.8,5.6 Hz,1H),4.09(dd,J=3.2,1.2 Hz,1H),3.67-3.46(m,2H),3.29(s,3H),2.83(s,3H).

[0255] Example 94 5-Chloro-2-(N-ethylcarbamoyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(N-ethylcarbamoyl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (95 mg, 0.15 mmol) in DCM / TFA (6.33 mL, 18:1) was stirred overnight at rt, and then EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (40 mg, 49%). ESI-MS m / z calculation for [C 20 H 22 Cl2N6O5S2] [M+H] + :561.0;found:561.1. 1H NMR(400 MHz,Methanol-d4)δ 8.63(s,1H),8.40(dd,J=4.4,2.0 Hz,2H),7.47(s,1H),6.39(d,J=5.2 Hz,1H),5.17(dd,J=11.2,3.2 Hz,1H),4.68(dd,J=11.2,5.6 Hz,1H),4.38(t,J=6.0 Hz,1H),4.19(d,J=2.4 Hz,1H),3.73-3.64(m,2H),3.44-3.20(m,2H),3.38(s,3H),1.25-1.21(m,3H).

[0256] Example 95 5-Chloro-2-(N-methylcarbamoyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-(N-methylcarbamoyl)pyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (80 mg, 0.12 mmol) in DCM / TFA (10 mL, 19:1) was stirred overnight at rt, and then EtN was added to neutralize the TFA. The mixture was concentrated and purified by preparative HPLC [MeCN / HO (10 mmol / L NHHCO), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the title compound (47.1 mg, 68%). ESI-MS m / z calculation for [C 20 H 22 Cl2N6O5S2] [M+H] + :561.0;found:561.2. 1H NMR(400 MHz,Methanol-d4)δ 8.88(s,1H),8.70-8.58(m,2H),7.71(s,1H),6.61(d,J=5.6 Hz,1H),5.43(dd,J=11.2,2.8 Hz,1H),5.03(dd,J=11.2,5.6 Hz,1H),4.62(t,J=6.0 Hz,1H),4.45(d,J=2.0 Hz,1H),4.10-3.84(m,3H),3.75-3.63(m,1H),3.17(s,3H),1.26(t,J=6.8 Hz,3H).

[0257] Example 96 5-Chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of copper(II) sulfate pentahydrate (4.4 mg, 0.018 mmol) and sodium (+)-L-ascorbate (7.0 mg, 0.035 mmol) in water (0.6 mL) was added to a solution of 5-chloro-2-cyanophenyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (80 mg, 0.18 mmol), 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (57 mg, 0.26 mmol), and KCO (243 mg, 1.76 mmol) in MeOH / THF (8 mL). The mixture was stirred at 50 °C for 18 h, then concentrated and partitioned between EtOAc and water. The organic phase was dried, evaporated, and analyzed by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA) to give the title compound (32 mg, 35%). ESI-MS m / z calcd for [C 19 H 17 Cl2N5O4S2] [M+H] + :514.0;found:514.0. 1H NMR(500 MHz,Methanol-d4)δ 8.65(s,1H),8.01(d,J=2.0 Hz,1H),7.77(d,J=8.4 Hz,1H),7.51(dd,J=8.4,2.0 Hz,1H),7.47(s,1H),6.41(d,J=5.3 Hz,1H),5.12(dd,J=11.3,2.9 Hz,1H),4.70(dd,J=11.3,5.3 Hz,1H),4.45(t,J=6.2 Hz,1H),4.23(d,J=2.8 Hz,1H),3.70(dd,J=11.5,5.5 Hz,1H),3.65(dd,J=11.5,6.7 Hz,1H),3.47(s,3H).

[0258] Example 97 1,3-Benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 1,3-benzothiazol-6-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (100 mg, 0.27 mmol), CuI (10 mg, 0.54 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (73 mg, 0.34 mmol) in MeCN (2.0 mL) was added DIPEA (0.14 mL, 0.81 mmol), and the mixture was stirred at 50 °C for 2 h. The mixture was analyzed by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (63 mg, 45%). ESI-MS m / z calcd for [C 19 H 18 ClN5O4S3] [M+H] + :512.0;found:512.0. 1H NMR(500 MHz,Methanol-d4)δ 9.26(s,1H),8.64(s,1H),8.40(d,J=1.5 Hz,1H),8.03(d,J=8.5 Hz,1H),7.80(dd,J=8.5,1.8 Hz,1H),7.47(s,1H),6.18(d,J=5.3 Hz,1H),5.10(dd,J=11.4,2.9 Hz,1H),4.64(dd,J=11.4,5.3 Hz,1H),4.59(t,J=6.3 Hz,1H),4.22(d,J=2.1 Hz,1H),3.73(dd,J=11.5,5.5 Hz,1H),3.69(dd,J=11.5,6.7 Hz,1H),3.43(s,3H).

[0259] Example 98 1,3-Benzothiazol-6-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 1,3-benzothiazol-6-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (100 mg, 0.27 mmol), CuI (10 mg, 0.54 mmol), and 4-(2-trimethylsilylethynyl)thiazol-2-ol (67 mg, 0.34 mmol) in MeCN (2.0 mL) was added DIPEA (0.14 mL, 0.81 mmol), and the mixture was stirred at 50 °C for 3 h. The mixture was analyzed by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (35 mg, 26%). ESI-MS m / z calcd for [C 19 H 19 N5O5S3] [M+H] + :494.1;found:494.1. 1H NMR(500 MHz,Methanol-d4)δ 9.26(s,1H),8.40(d,J=1.6 Hz,1H),8.37(s,1H),8.04(d,J=8.5 Hz,1H),7.79(dd,J=8.5,1.8 Hz,1H),6.71(s,1H),6.16(d,J=5.3 Hz,1H),5.06(dd,J=11.4,2.9 Hz,1H),4.59-4.54(m,2H),4.20(d,J=2.1 Hz,1H),3.72(dd,J=11.5,5.5 Hz,1H),3.68(dd,J=11.5,6.7 Hz,1H),3.42(s,3H).

[0260] Example 99 1,3-Benzothiazol-6-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 1,3-benzothiazol-6-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (100 mg, 0.27 mmol), CuI (10 mg, 0.54 mmol), and 4-(2-trimethylsilylethynyl)thiazol-2-amine (67 mg, 0.34 mmol) in MeCN (2.0 mL) was added DIPEA (0.14 mL, 0.81 mmol), and the mixture was stirred at 50 °C for 2 h. The mixture was analyzed by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (96 mg, 72%). ESI-MS m / z calcd for [C 19 H 20 N6O4S3] [M+H] + :493.1;found:493.1. 1H NMR(500 MHz,Methanol-d4)δ 9.28(s,1H),8.59(s,1H),8.42(d,J=1.5 Hz,1H),8.06(d,J=8.5 Hz,1H),7.81(dd,J=8.5,1.7 Hz,1H),7.16(s,1H),6.21(s,1H),5.14(s,1H),4.68-4.56(m,2H),4.26(s,1H),3.77-3.69(m,2H),3.45(s,3H).

[0261] Example 100 5-Cyano-1,3-benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-cyano-1,3-benzothiazol-6-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (37 mg, 0.094 mmol), CuI (3.6 mg, 0.019 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (30 mg, 0.14 mmol) in MeCN (1.5 mL) was added EtN (52 μL, 0.38 mmol) and TBAF (9.4 μL, 1 M in THF, 0.0094 mmol), and the mixture was stirred at 50 °C for 1 h. The mixture was filtered and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA) to give the title compound (43 mg, 48%). ESI-MS m / z calcd for [C 20 H 17 ClN6O4S3] [M+H] + :537.0;found:537.0. 1H NMR(500 MHz,Methanol-d4)δ 9.41(s,1H),8.67(s,1H),8.65(s,1H),8.53(s,1H),7.47(s,1H),6.35(d,J=5.3 Hz,1H),5.16(dd,J=11.3,2.9 Hz,1H),4.70(dd,J=11.3,5.3 Hz,1H),4.57(t,J=6.1 Hz,1H),4.23(d,J=2.5 Hz,1H),3.71-3.63(m,2H),3.52(s,3H).

[0262] Example 101 Thiazolo[4,5-b]pyridin-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of thiazolo[4,5-b]pyridin-6-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (112 mg, 0.30 mmol), CuI (11.5 mg, 0.061 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (98 mg, 0.46 mmol) in MeCN (3.0 mL) was added EtN (0.17 mL, 1.21 mmol) and TBAF (30 μL, 1 M in THF, 0.030 mmol), and the mixture was stirred at 50 °C for 2.5 h. The mixture was filtered and purified by preparative HPLC (C). 18 The resulting product was further purified by chromatography (SiO, EtOAc / MeOH) to give the title compound (2.1 mg, 1%). ESI-MS m / z calcd for [C 18 H 17 ClN6O4S3] [M+H] + :513.0;found:513.0. 1H NMR(500 MHz,Methanol-d4)δ 9.59(s,1H),8.95(d,J=2.1 Hz,1H),8.91(d,J=2.0 Hz,1H),8.66(s,1H),7.49(s,1H),6.25(d,J=5.3 Hz,1H),5.15(dd,J=11.4,2.8 Hz,1H),4.68(dd,J=11.3,5.2 Hz,1H),4.60(t,J=6.0 Hz,1H),4.26-4.22(m,1H),3.73(d,J=6.1 Hz,2H),3.47(s,3H).

[0263] Example 102 5-Methylsulfanylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (50 mg, 0.094 mmol) in DMF (1.0 mL) was added sodium thiomethoxide (33 mg, 0.47 mmol), and the mixture was stirred at rt for 22 h. The mixture was partitioned between EtOAc and water. The organic phase was dried, evaporated, and purified by preparative HPLC (C 18 , HO / MeCN / 0.1%TFA) to give the title compound (7 mg, 15%). ESI-MS m / z calculated for [C 18 H 20 ClN5O4S3] [M+H] + :502.0;found:502.0. 1H NMR(500 MHz,Methanol-d4)δ 8.66(s,1H),8.60(s,1H),8.47-8.43(m,1H),8.25(t,J=2.0 Hz,1H),7.49(s,1H),6.36(d,J=5.3 Hz,1H),5.12(dd,J=11.3,2.9 Hz,1H),4.68(dd,J=11.3,5.3 Hz,1H),4.48(t,J=6.1 Hz,1H),4.22(d,J=2.3 Hz,1H),3.76-3.69(m,2H),3.44(s,3H),2.64(s,3H).

[0264] Example 103 5-(Trifluoromethylsulfanyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-(trifluoromethylsulfanyl)pyridin-3-yl 3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (39 mg, 0.095 mmol), CuI (3.6 mg, 0.019 mmol), and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (31 mg, 0.14 mmol) in MeCN (1.5 mL) was added EtN (53 μL, 0.38 mmol) and TBAF (9.5 μL, 1 M in THF, 0.0095 mmol), and the mixture was stirred at 50 °C for 2 h. The mixture was filtered and purified by preparative HPLC (C). 18 , HO / MeCN / 0.1%TFA) to give the title compound (38 mg, 72%). ESI-MS m / z calcd for [C 18 H 17 ClF3N5O4S3] [M+H] + :556.0;found:556.0. 1H NMR(500 MHz,Methanol-d4)δ 8.93(d,J=2.0 Hz,1H),8.74(d,J=1.8 Hz,1H),8.66(s,1H),8.48(t,J=1.9 Hz,1H),7.49(s,1H),6.35(d,J=5.3 Hz,1H),5.13(dd,J=11.3,2.9 Hz,1H),4.69(dd,J=11.3,5.3 Hz,1H),4.48(t,J=6.2 Hz,1H),4.24(d,J=2.4 Hz,1H),3.73(dd,J=11.4,5.4 Hz,1H),3.67(dd,J=11.4,6.8 Hz,1H),3.44(s,3H).

[0265] Intermediate 1 O-Ethyl(3,5-dichloro-4-fluorophenyl)sulfanylmethanethioate [ka] 3,5-Dichloro-4-fluoroaniline (6.70 g, 37.2 mmol) was suspended in HCl / HO (V / V = 1:4, 100 mL) and the suspension was cooled to -5 °C. A solution of NaNO (5.14 g, 74.4 mmol) in HO (20 mL) was added dropwise to the suspension. The mixture was stirred at -5 °C until the solution became clear (2-3 h). The mixture was then added to a solution of potassium ethyl xanthate (17.90 g, 112 mmol) in HO (50 mL). The mixture was stirred at 50 °C for 3 h and then extracted with EtOAc (3 × 100 mL). The combined organic phases were dried over NaSO, concentrated, and purified by column chromatography (PE, Silica-CS 80 g, 40 mL / min, silica gel, UV254) to give the product (7.30 g, 60%). 1 H NMR(400 MHz,Methanol-d4)δ 7.67(d,J=6.3 Hz,2H),4.66(q,J=7.1 Hz,2H),1.36(t,J=7.1 Hz,3H).

[0266] 3,5-Dichloro-4-fluorobenzenethiol [ka] To a solution of O-ethyl(3,5-dichloro-4-fluorophenyl)sulfanylmethanethioate (7.30 g, 22.3 mmol) in MeOH (50 mL) was added NaOH (22 mL, 2 M), and the mixture was stirred at 70 °C for 2 h. Most of the MeOH was removed by evaporation, and the remaining solution was extracted with EtOAc (100 mL). The aqueous layer was acidified with aqueous NaHSO and extracted with EtOAc (100 mL) and diethyl ether (2 × 100 mL). The combined organic phases were dried and evaporated to give the product (4.60 g, 88%). 1 H NMR(400 MHz,DMSO)δ 7.58(d,J=5.0 Hz,2H),6.03(s,1H).

[0267] 2,4,6-Tri-O-acetyl-3-azido-3-deoxy-β-D-galactopyranosyl chloride [ka] A solution of 1,2,4,6-tetra-O-acetyl-3-azido-3-deoxy-β-D-galactopyranoside (12.0 g, 32.1 mmol), PCl5 (7.5 g, 36.0 mmol), and boron trifluoride diethyl etherate (50 μL, 0.41 mmol) in DCM (150 mL) was stirred at rt for 1 h. The mixture was partitioned between saturated aqueous NaHCO3 and DCM. The organic phase was dried and concentrated, and the residue was triturated with diethyl ether / PE to give the product as a crystalline solid (10.2 g, 91%). 1 H NMR(400 MHz,Chloroform-d)δ 5.48(d,J=3.2 Hz,1H),5.34(t,J=9.2 Hz,1H),5.24(d,J=8.7 Hz,1H),4.18(dd,J=11.5,6.1 Hz,1H),4.10(dd,J=11.6,6.7 Hz,1H),3.98(t,J=6.4 Hz,1H),3.60(dd,J=10.3,3.3 Hz,1H),2.20(s,3H),2.17(s,3H),2.07(s,3H).

[0268] 3,5-Dichloro-4-fluorophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 2,4,6-tri-O-acetyl-3-azido-3-deoxy-β-D-galactopyranosyl chloride (6.20 g, 17.7 mmol) and 3,5-dichloro-4-fluorobenzenethiol (3.77 g, 19.1 mmol) in DMF (20 mL) was added CsCO (17.3 g, 53.2 mmol), and the mixture was stirred at room temperature for 2 h. Water (60 mL) was added, and the mixture was extracted with EtOAc (50 mL). The organic phase was evaporated and purified by column chromatography (PE / EtOAc = 10 / 1 to 5 / 1, Silica-CS 120 g, 40 mL / min, silica gel, UV254). Further purification by reverse-phase chromatography (MeCN / HO = 1 / 20 to 3 / 1, C-18 column, 20 mL / min, UV254) afforded the product (2.2 g, 24%). ESI-MS m / z calculation for [C 18 H 18 Cl2FN3O7S] [M+NH4] + :527.0;found:527.0. 1 H NMR(400 MHz,CDCl3)δ 7.40(t,J=18.0 Hz,2H),5.86(d,J=5.5 Hz,1H),5.41(d,J=2.7 Hz,1H),5.26-5.07(m,1H),4.54(dd,J=7.7,4.6 Hz,1H),4.13-4.03(m,1H),4.03-3.90(m,1H),3.84(dd,J=11.0,3.3 Hz,1H),2.11(d,J=11.0 Hz,6H),2.04-1.90(m,3H).

[0269] 3,5-Dichloro-4-fluorophenyl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 3,5-dichloro-4-fluorophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (2.20 g, 4.31 mmol) in MeOH / EtN / HO (18 mL, 5:3:1) was stirred at rt overnight. The mixture was evaporated and purified by preparative HPLC (MeCN / HO (10 mmol / L NHHCO = 30-90%, X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the product (860 mg, 52%). ESI-MS m / z calculation for [C 12 H 12 Cl2FN3O4S] [M+NH4] + :401.0;found:401.0. 1 H NMR(400 MHz,Methanol-d4)δ 7.66(d,J=6.3 Hz,2H),5.64(d,J=5.5 Hz,1H),4.36(dd,J=10.8,5.5 Hz,1H),4.24(t,J=5.9 Hz,1H),4.02(d,J=2.1 Hz,1H),3.74-3.60(m,2H),3.47(dd,J=10.8,2.9 Hz,1H).

[0270] 3,5-Dichloro-4-fluorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a stirred solution of 3,5-dichloro-4-fluorophenyl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside (510 mg, 1.33 mmol) in DMF (10 mL) was added benzaldehyde dimethyl acetal (444 mg, 2.92 mmol), followed by D(+)-10-camphorsulfonic acid (67.8 mg, 0.29 mmol). The mixture was stirred at 50°C under vacuum using a water pump for 3 hours. The mixture was added dropwise to aqueous NaHCO3 (100 mL), and the solution was filtered. The resulting white solid was dried in vacuo to give the product (600 mg, 96%). ESI-MS m / z calculation for [C 19 H 16 Cl2FN3O4S] [M+H] + :472.0;found:472.0. 1 H NMR(400 MHz,Methanol-d4)δ 7.52(d,J=6.2 Hz,2H),7.39(d,J=3.7 Hz,2H),7.25(dd,J=5.1,1.9 Hz,3H),5.71(d,J=5.2 Hz,1H),5.57(s,1H),4.80(m,1H),4.40(dd,J=10.9,5.1 Hz,1H),4.34(d,J=3.0 Hz,1H),4.06(d,J=7.6 Hz,1H),3.96(d,J=12.6 Hz,1H),3.50(dd,J=10.9,3.2 Hz,1H).

[0271] 3,5-Dichloro-4-fluorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,5-dichloro-4-fluorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (300 mg, 0.64 mmol) in DMF (5 mL) was added NaH (60% in oil, 73.0 mg, 1.91 mmol). The mixture was stirred for 30 min, and then iodomethane (79.1 μL, 1.27 mmol) was added dropwise. The mixture was stirred at rt for 1 h and then poured into water (15 mL). The solution was extracted with EtOAc, and the organic phase was evaporated to give the product (300 mg, 97%). ESI-MS m / z calcd for [C 20 H 18 Cl2FN3O4S] [M+H] + :486.0;found:486.0. 1 H NMR(400 MHz,CDCl3)δ 7.45(dd,J=7.5,2.0 Hz,2H),7.37(t,J=4.6 Hz,2H),7.34-7.25(m,3H),5.91(d,J=5.2 Hz,1H),5.56(s,1H),4.26(d,J=2.7 Hz,1H),4.18(ddd,J=8.0,5.6,3.4 Hz,2H),4.12-3.97(m,2H),3.60(dd,J=10.7,3.3 Hz,1H),3.50-3.45(m,3H).

[0272] 3,5-Dichloro-4-fluorophenyl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 3,5-dichloro-4-fluorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (135 mg, 0.28 mmol) in DMF (5 mL), trimethyl(2-thiazol-2-ylethynyl)silane (75.5 mg, 0.42 mmol), sodium (+)-L-ascorbate (55.0 mg, 0.28 mmol), and copper(II) sulfate pentahydrate (70.0 mg, 0.28 mmol) were added, and the mixture was stirred at RT for 6 h. The mixture was concentrated and purified by column chromatography (PE / EtOAc = 10 / 0 to 1 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (76 mg, 46%). ESI-MS m / z calculation for [C 25 H 21 Cl2FN4O4S2] [M+H] + :595.0;found:595.0. 1 H NMR(400 MHz,DMSO-d6)δ 8.82(s,1H),7.89-7.75(m,4H),7.39-7.34(m,5H),6.63(d,J=5.2 Hz,1H),5.58(s,1H),5.16(dd,J=11.2,2.8 Hz,1H),4.84(dd,J=11.6,5.2 Hz,1H),4.58(d,J=2.8 Hz,1H),4.11(s,1H),4.09(d,J=12.4 Hz,1H),3.92(d,J=11.6 Hz,1H),3.34(s,3H).

[0273] Intermediate 2 5-Bromopyridin-3-yl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 2,4,6-tri-O-acetyl-3-azido-3-deoxy-β-D-galactopyranosyl chloride (1.20 g, 3.43 mmol) and 5-bromopyridine-3-thiol (1.30 g, 6.86 mol) in DMF (10 mL), CsCO (4.47 g, 13.7 mol) was added, and the mixture was stirred at room temperature overnight. The mixture was concentrated and purified by column chromatography (10-60% EtOAc / PE, Silica-CS 20 g, 30 mL / min, silica gel, UV254) to give the product (1.25 g, 72%). ESI-MS m / z calculation for [C 17 H 19 BrNOS] [M+H] + :503.0;found:503.0. 1 H NMR(400 MHz,CDCl3)δ 8.50(dd,J=10.7,2.0 Hz,2H),7.90(t,J=2.0 Hz,1H),5.91(d,J=5.5 Hz,1H),5.42(d,J=2.7 Hz,1H),5.22(dd,J=10.9,5.5 Hz,1H),4.56(dd,J=7.6,4.6 Hz,1H),4.15-4.00(m,1H),3.92(ddd,J=14.3,11.3,5.6 Hz,2H),2.12(d,J=13.2 Hz,6H),1.97(s,3H).

[0274] 5-Bromopyridin-3-yl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromopyridin-3-yl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (300 mg, 0.60 mmol) in MeOH / EtN / HO (0.9 mL, 5:3:1) was stirred at rt for 4 h. The mixture was evaporated and purified by preparative HPLC (X-Select 10 μm 19*250 mm, 20 mL / min, MeOH / HO (10 mmol / L NHHCO) = 40-95%) to give the product (208 mg, 93%). ESI-MS m / z calculation for [C 11 H 13 BrN4O4S] [M+H] + :377.0,found:377.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.52(d,J=1.8 Hz,1H),8.43(d,J=2.0 Hz,1H),8.16(t,J=2.0 Hz,1H),5.63(d,J=5.4 Hz,1H),4.29(dd,J=10.8,5.4 Hz,1H),4.15(t,J=6.0 Hz,1H),3.95(d,J=2.1 Hz,1H),3.61-3.52(m,2H),3.42(dt,J=14.5,7.3 Hz,1H).

[0275] 5-Bromopyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromopyridin-3-yl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside (208 mg, 0.55 mmol) in DMF (3 mL), D(+)-10-camphorsulfonic acid (25.6 mg, 0.11 mmol) and benzaldehyde dimethyl acetal (168 mg, 1.10 mmol) were added, and the mixture was stirred at 50 °C under reduced pressure for 5 h. The mixture was partitioned between water (10 mL) and DCM (15 mL). The aqueous phase was extracted with DCM (3 × 5 mL), and the combined organic phases were dried and evaporated. The resulting material was dissolved in DMF (3 mL) and cooled to 0 °C. NaH (60% in oil, 21.2 mg, 0.92 mol) was added, and the mixture was stirred for 30 min. Iodomethane (197 mg, 1.39 mol) was slowly added, and the mixture was stirred at rt for 2 h. Water (10 mL) and DCM (15 mL) were added, and the aqueous layer was extracted with DCM (3 × 5 mL). The combined organic layers were dried over NaSO, concentrated, and purified by column chromatography (EA / PE = 0-40%, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (200 mg, 76%). ESI-MS m / z calculation for [C 19 H 19 BrN4O4S] [M+H] + :479.0,found:479.0. 1 H NMR(400 MHz,CDCl3)δ 8.01-7.90(m,1H),7.51-7.38(m,3H),7.38-7.25(m,4H),5.97(d,J=5.1 Hz,1H),5.55(s,1H),4.26(d,J=3.1 Hz,1H),4.19(dd,J=10.7,5.1 Hz,2H),4.08-4.06(m,1H),4.04(s,1H),3.67-3.63(m,1H),3.50(d,J=5.7 Hz,3H).

[0276] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromopyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (200 mg, 0.42 mmol) in DMF (5 mL) was added trimethyl(2-thiazol-2-ylethynyl)silane (113 mg, 0.63 mmol), copper(II) sulfate pentahydrate (51.9 mg, 0.21 mmol), and sodium (+)-L-ascorbate (82.6 mg, 0.42 mmol), and the mixture was stirred at RT for 3 h. The mixture was partitioned between water (10 mL) and DCM (10 mL), and the aqueous phase was extracted with DCM (2 × 5 mL). The combined organic phase was washed with water (20 mL) and brine (20 mL), dried over NaSO, evaporated, and purified by column chromatography (EA / PE = 10-70%, Silica-CS 4 g, 12 mL / min, silica gel, UV254) to give the product (200 mg, 82%). ESI-MS m / z calculation for [C 24 H 22 BrNOS2] [M+H] + :588.0,found:588.0. 1 H NMR(400 MHz,CDCl3)δ 8.39(s,1H),7.96(d,J=8.7 Hz,2H),7.64(dt,J=7.2,3.6 Hz,1H),7.46(dd,J=5.8,3.3 Hz,1H),7.37-7.26(m,6H),6.12(d,J=4.5 Hz,1H),5.46(s,1H),5.31-5.21(m,1H),4.61-4.45(m,2H),4.24(t,J=6.7 Hz,2H),4.11(s,1H),3.36(s,3H).

[0277] Intermediate 3 3-Azido-4,6-O-benzylidene-3-deoxy-D-galactopyranose [ka] To a solution of 3-azido-3-deoxy-D-galactopyranose (Lowary, T.L.; Hindsgaul, O. Recognition of Synthetic O-Methyl, Epimeric, and Amino Analogues of the Acceptor α-L-Fucp-(1→2)-β-D-Galp-or Glycosyltransferases. Carbohydrate Research 1994, 251, 33-67) (16.4 g, 79.9 mmol) in DMF (120 mL) was added benzaldehyde dimethyl acetal (18.2 g, 120 mmol), followed by D(+)-10-camphorsulfonic acid (3.71 g, 16.0 mmol). The mixture was stirred at 50°C for 4 h. The mixture was added dropwise to saturated aqueous NaHCO3 (200 mL). The mixture was filtered and the white solid was washed with water and dried in vacuo to give the product (15.0 g, 64%, α / β=1:1). 3-Azido-4,6-O-benzylidene-3-deoxy-α-D-galactopyranose 1 H NMR(400 MHz,CD3OD)δ 7.51-7.53(m,2H),7.35-7.39(m,3H),5.65(s,1H),5.25(d,J=3.2 Hz,1H,H-1α),3.35-3.45(m,6H). 3-Azido-4,6-O-benzylidene-3-deoxy-β-D-galactopyranose 1 H NMR(400 MHz,CD3OD)δ 7.51-7.53(m,2H),7.35-7.39(m,3H),5.65(s,1H),4.58(d,J=7.6 Hz,1H,H-1β),3.35-3.45(m,6H).

[0278] Methyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-D-galactopyranoside [ka] To a solution of 3-azido-4,6-O-benzylidene-3-deoxy-D-galactopyranose (5.00 g, 17.0 mmol) in DMF (40 mL) was added NaH (60% in oil, 1.96 g, 51.1 mmol) under a nitrogen atmosphere at 0 °C, and the mixture was stirred for 20 min. Iodomethane (3.18 mL, 51.1 mmol) was added, and the mixture was stirred at rt for 1 h. After dilution with water (50 mL), the mixture was extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine, dried over NaSO, and concentrated in vacuo. The residue was purified by column chromatography (PE / EtOAc = 10 / 1 to 1 / 1, Silica-CS 20 g, 25 mL / min, silica gel, UV 254) to give the product (5.10 g, 93%, α / β = 0.5:1). Methyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-α-D-galactopyranoside 1 H NMR(400 MHz,CD3OD)δ 7.42-7.44(m,2H),7.27-7.29(m,3H),5.56(s,1H),4.99(d,J=3.2 Hz,1H,H-1α),3.62-4.27(m,4H),3.44(s,3H),3.39(s,3H),3.32-3.40(m,1H),3.23-3.25(m,1H). Methyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-β-D-galactopyranoside 1 H NMR(400 MHz,CD3OD)δ 7.42-7.44(m,2H),7.27-7.29(m,3H),5.55(s,1H),4.31(d,J=7.6 Hz,1H,H-1β),3.62-4.27(m,4H),3.51(s,3H),3.49(s,3H),3.32-3.40(m,1H),3.23-3.25(m,1H).

[0279] Acetyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-D-galactopyranoside [ka] To a solution of methyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-D-galactopyranoside (5.10 g, 15.9 mmol) in acetic anhydride (40.0 mL) and acetic acid (20 mL) was added dropwise concentrated H2SO4 at 0 °C. The mixture was stirred at 0 °C for 4 h and subsequently added dropwise to saturated aqueous NaHCO3. The mixture was extracted with DCM (3 × 100 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (PE / EtOAc = 10 / 1 to 1 / 1, Silica-CS 4 g, 12 mL / min, silica gel, UV 254). The resulting material was suspended in EtOAc (4.00 mL). The mixture was heated to 60 °C, then cooled to 25 °C, and n-heptane (20.0 mL) was added with stirring. The mixture was cooled to 0° C., stirred for 1 h, filtered and washed with n-heptane / EtOAc (4:1, 10 mL) to give the product (1.2 g) as a white solid that was used directly in the next step. 1 H NMR(400 MHz,CDCl3)δ 6.38(d,J=3.6 Hz,1H),5.33(dd,J=3.2,1.2 Hz,1H),4.14-4.17(m,1H),3.91-4.03(m,2H),3.80(dd,J=6.4,3.2 Hz,1H),3.62(dd,J=10.4,3.6 Hz,1H),3.43(s,3H),2.11(s,3H),2.10(s,3H),1.98(s,3H).

[0280] Acetyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside [ka] To a solution of acetyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-D-galactopyranoside (1.17 g, 3.39 mmol) in DCM (15 mL) was added PCl (1.06 g, 5.08 mmol), followed by boron trifluoride diethyl etherate (0.209 mL, 1.69 mmol) at 30 °C under a nitrogen atmosphere. The mixture was stirred at 30 °C for 30 min and then added dropwise to saturated aqueous NaHCO solution. The mixture was extracted with DCM (3 × 100 mL). The combined The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was dissolved in DMF (4.0 mL), and potassium thioacetate (731 mg, 6.4 mmol) was added. The mixture was stirred overnight at rt under a nitrogen atmosphere. After dilution with water (50 mL), the mixture was extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (PE / EtOAc = 10 / 1 to 3 / 1, Silica-CS 20 g, 18 mL / min, silica gel, UV 254) to give the product (1.15 g, 75%, α / β = 0.23:1). Acetyl 4,6-di-O-acetyl-3-azido-2-O-methyl-3-deoxy-1-thio-α-D-galactopyranoside 1 H NMR(400 MHz,CDCl3)δ 6.25(d,J=5.2 Hz,1H,H-1α),5.27-5.29(m,1H),3.85-4.08(m,4H),3.42-3.45(m,1H),3.39(s,3H),2.39(s,3H),2.09(s,3H),1.97(s,3H). Acetyl 4,6-di-O-acetyl-3-azido-2-O-methyl-3-deoxy-1-thio-β-D-galactopyranoside 1H NMR(400 MHz,CDCl3)δ 5.32-5.33(m,1H),5.04(d,J=10.0 Hz,1H,H-1β),3.85-4.08(m,3H),3.57(dd,J=9.2,3.2 Hz,1H),3.52(s,3H),3.33(t,J=9.6 Hz,1H),2.36(s,3H),2.08(s,3H),1.97(s,3H).

[0281] 5-Bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside [ka] To a solution of acetyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside (210 mg, 0.58 mmol) and 5-bromo-3-fluoropyridine-2-carbonitrile (175 mg, 0.87 mmol) in DMF (4.0 mL) was added diethylamine (85.0 mg, 1.16 mmol), and the mixture was stirred at rt for 1 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine, dried over NaSO, and concentrated. The residue was purified by column chromatography (PE / EA = 10 / 1 to 3 / 1, Silica-CS 4 g, 12 mL / min, silica gel, UV 254) to give the product (180 mg, 62%, α / β = 0.3:1). ESI-MS m / z calculation for [C 17 H 18 BrNOS] [M+H] + :500.0,found:500.0. 5-Bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside 1H NMR(400 MHz,CDCl3)δ 8.57-8.58(m,1H),8.13(d,J=2.0 Hz,1H),6.05(d,J=5.2 Hz,1H),5.35(d,J=3.2 Hz,1H),4.41-4.44(m,1H),3.78-4.08(m,3H),3.54(s,3H),3.34-3.44(m,1H),2.09(s,3H),1.98(s,3H). 5-Bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-β-D-galactopyranoside 1 H NMR(400 MHz,CDCl3)δ 8.57-8.58(m,1H),8.18(d,J=2.0 Hz,1H),5.33(dd,J=3.2,1.2 Hz,1H),4.68(d,J=9.2 Hz,1H),3.78-4.08(m,3H),3.63(s,3H),3.55-3.57(m,1H),3.34-3.44(m,1H),2.12(s,3H),2.01(s,3H).

[0282] 5-Bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-deoxy-2-O-methyl-3-[4-(thiazol-2-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside (240 mg, 0.48 mmol) and trimethyl(2-thiazol-2-ylethynyl)silane (217 mg, 1.20 mmol) in DMF (6.0 mL) was added copper(II) sulfate pentahydrate (59.9 mg, 0.24 mmol) and sodium (+)-L-ascorbate (95.0 mg, 0.48 mmol), and the mixture was stirred at room temperature for 3 hours. The mixture was diluted with water (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA = 10 / 1 to 1 / 1, Silica-CS 4 g, 12 mL / min, silica gel, UV254). The resulting product was further purified by preparative SFC to give the product (57.0 mg, 20%). ESI-MS m / z calculation for [C 22 H 21 BrN6O6S2] [M+H] + :609.0;found:609.0. 1 H NMR(400 MHz,CDCl3)δ 8.60(d,J=2.0 Hz,1H),8.20(d,J=2.0 Hz,1H),8.16(s,1H),7.78(d,J=3.2 Hz,1H),7.30(d,J=3.6 Hz,1H),6.26(d,J=5.6 Hz,1H),5.58(d,J=2.0 Hz,1H),4.99(dd,J=11.2,3.2 Hz,1H),4.76(dd,J=11.2,5.2 Hz,1H),4.64-4.67(m,1H),3.96-4.04(m,2H),3.39(s,3H),2.01(s,3H),1.90(s,3H).

[0283] Intermediate 4 Acetyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-azido-3-deoxy-β-D-galactopyranosyl chloride (4.0 g, 11.4 mmol) and potassium thioacetate (2.02 g, 17.1 mmol) in DMF (25 mL) was stirred at 40 °C for 1 h. The mixture was partitioned between EtOAc and saturated aqueous NaHCO , and the organic phase was separated, dried, and evaporated. The residue was purified by chromatography (SiO , PE / EtOAc) to give the product (2.90 g, 52%). ESI-MS m / z calcd for [C 14 H 19 N3O8S] [M+Na] + :412.1;found:411.9. 1 H NMR(400 MHz,Chloroform-d)δ 6.25(d,J=5.3 Hz,1H),5.43(d,J=2.9 Hz,1H),5.40(dd,J=11.0,5.3 Hz,1H),4.16-3.97(m,3H),3.71(dd,J=10.9,3.3 Hz,1H),2.43(s,3H),2.16(s,3H),2.08(s,3H),2.04(s,3H).

[0284] 2-Bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of acetyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (1.30 g, 3.34 mmol) and 2-bromo-5-chloro-3-fluoropyridine (843 mg, 4.01 mmol) in DMF (6 mL) was added diethylamine (488 mg, 6.68 mmol), and the mixture was stirred at room temperature overnight. After dilution with water (15 mL), the mixture was extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine (20 mL), dried over NaSO, concentrated, and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 20 g, 20 mL / min, silica gel, UV254) to give the product as a white solid (770 mg, 43%). ESI-MS m / z calculation for [C 17 H 18 BrClN4O7S] [M+H] + :537.0;found:537.0. 1 H NMR(400 MHz,CDCl3)δ 8.13(d,J=2.4 Hz,1H),7.76(d,J=2.4 Hz,1H),6.05(d,J=5.6 Hz,1H),5.43(t,J=6.2 Hz,1H),5.27(dd,J=11.0,5.6 Hz,1H),4.47(dd,J=7.4,5.1 Hz,1H),4.08-4.01(m,1H),3.96(dq,J=7.9,5.6 Hz,2H).

[0285] 2-Bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2-bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (770 mg, 1.43 mmol) in MeOH (5.0 mL) and a catalytic amount of NaOMe was stirred at rt for 20 min. The mixture was neutralized with an acid ion resin and filtered. The filtrate was concentrated, and the resulting material was dissolved in DMF (5 mL). Benzaldehyde dimethyl acetal (404 mg, 2.65 mmol) was added, followed by D(+)-10-camphorsulfonic acid (30.8 mg, 0.13 mmol), and the mixture was stirred at 50 °C under vacuum using a water pump for 4 h. After cooling to rt, the mixture was diluted with water (15 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were concentrated and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (300 mg, 42%). ESI-MS m / z calculation for [C 18 H 16 BrClN4O4S] [M+H] + :499.0,found:499.0. 1 H NMR(400 MHz,CDCl3)δ 8.09(d,J=2.3 Hz,1H),7.82(d,J=2.3 Hz,1H),7.45(dd,J=7.5,1.9 Hz,2H),7.38-7.27(m,3H),5.91(d,J=5.3 Hz,1H),5.58(s,1H),4.64(dt,J=10.8,5.4 Hz,1H),4.36(d,J=3.0 Hz,1H),4.18(dd,J=12.8,1.4 Hz,1H),4.07-3.97(m,2H),3.65(dd,J=10.8,3.3 Hz,1H),2.59(d,J=5.7 Hz,1H).

[0286] 2-Bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 2-bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (300 mg, 0.60 mmol) in DMF (8.0 mL) was added silver(I) oxide (696 mg, 3.00 mmol), followed by iodomethane (426 mg, 3.00 mmol). The mixture was stirred at rt for 48 h and filtered. The filtrate was evaporated and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (240 mg, 78%). ESI-MS m / z calculation for [C 19 H 18 BrClN4O4S] [M+H] + :513.0,found:513.0. 1 H NMR(400 MHz,CDCl3)δ 8.08(d,J=2.4 Hz,1H),7.81(t,J=3.6 Hz,1H),7.46(dd,J=7.5,1.9 Hz,2H),7.31(ddd,J=6.7,5.1,1.5 Hz,3H),6.09(d,J=5.2 Hz,1H),5.56(s,1H),4.28-4.21(m,2H),4.13(dd,J=12.7,1.5 Hz,1H),4.07-4.04(m,1H),3.96(s,1H),3.76(dd,J=10.6,3.3 Hz,1H),3.50(s,3H).

[0287] 5-Chloro-2-cyanopyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 2-bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (230 mg, 0.45 mmol) in DMF (4.0 mL) were added Zn (14.6 mg, 0.22 mmol), Zn(CN) (52.6 mg, 0.45 mmol), 1,1'-bis(diphenylphosphino)ferrocene (20.2 mg, 0.036 mmol), and tris(dibenzylideneacetone)dipalladium(0) (32.8 mg, 0.036 mmol), and the mixture was stirred at 100°C for 3 hours under a nitrogen atmosphere. The mixture was concentrated and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (105 mg, 51%). ESI-MS m / z calculation for [C 20 H 18 ClN5O4S] [M+H] + :460.1,found:460.0. 1 H NMR(400 MHz,CDCl3)δ 8.44(d,J=2.1 Hz,1H),7.98(d,J=2.1 Hz,1H),7.46-7.39(m,2H),7.32-7.25(m,3H),6.06(t,J=7.6 Hz,1H),5.56(d,J=7.2 Hz,1H),4.27(t,J=5.2 Hz,1H),4.21(dd,J=10.6,5.2 Hz,1H),4.12(dd,J=13.0,1.8 Hz,1H),4.06(d,J=4.4 Hz,2H),3.71(dd,J=10.6,3.3 Hz,1H),3.52(s,3H).

[0288] 5-Chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (130 mg, 0.28 mmol) and trimethyl(2-thiazol-2-ylethynyl)silane (103 mg, 0.57 mmol) in DMF (3 mL), sodium (+)-L-ascorbate (112 mg, 0.57 mmol) and copper(II) sulfate pentahydrate (35.3 mg, 0.14 mmol) were added, and the mixture was stirred at RT overnight. The mixture was evaporated and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 4 g, 12 mL / min, silica gel, UV254) to give the product (90 mg, 56%). ESI-MS m / z calculation for [C 25 H 21 ClN6O4S2] [M+H] + :569.1,found:569.0. 1 H NMR(400 MHz,CDCl3)δ 8.50(d,J=2.1 Hz,1H),8.24(s,1H),8.02(d,J=2.1 Hz,1H),7.78(s,1H),7.32(ddd,J=9.1,7.6,4.0 Hz,6H),6.21(d,J=5.1 Hz,1H),5.46(s,1H),5.27(dd,J=11.3,2.7 Hz,1H),4.57(dd,J=11.2,5.2 Hz,1H),4.52(d,J=2.2 Hz,1H),4.32(s,1H),4.19(d,J=11.8 Hz,1H),4.09(d,J=12.0 Hz,1H),3.34(s,3H).

[0289] Intermediate 5 2-Bromo-5-chloropyridin-3-yl 3-azido-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a cooled solution (0 °C) of 2-bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (630 mg, 1.27 mmol) in DMF (10 mL) was added CsCO (1.7 g, 5.0 mmol), and the mixture was stirred for 10 min. Benzyl bromide (0.31 mL, 2.54 mmol) was added, and the mixture was stirred at rt for 2 h. Water (50 mL) was added, and the mixture was extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine, dried over NaSO, concentrated, and purified by column chromatography (PE / EtOAc = 10 / 1 to 5 / 1, Silica-CS 12 g, 12 mL / min, silica gel, UV254) to give the product (460 mg, 62%). ESI-MS m / z calculation for [C 25 H 22 BrClN4O4S] [M+H] + :589.0;found:589.0. 1 H NMR(400 MHz,CDCl3)δ 8.07(d,J=2.4 Hz,1H),7.61(d,J=2.4 Hz,1H)7.45-7.42(m,2H),7.36-7.29(m,5H),7.26-7.21(m,3H),5.77(d,J=5.2 Hz,1H),5.55(s,1H),4.75(d,J=11.6 Hz,1H),4.66(d,J=11.6 Hz,1H),4.44(dd,J=5.6,10.8 Hz,1H),4.28(d,J=2.8 Hz,1H),4.12-4.01(m,2H),3.96(s,1H),4.82(dd,J=3.2,10.4 Hz,1H).

[0290] 5-Chloro-2-cyanopyridin-3-yl 3-azido-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 2-bromo-5-chloropyridin-3-yl 3-azido-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (460 mg, 0.78 mmol) in DMF (4.0 mL) was added Zn (25.4 mg, 0.39 mmol), Zn(CN) (182.5 mg, 1.56 mmol), 1,1'-bis(diphenylphosphino)ferrocene (34.6 mg, 0.062 mmol), and tris(dibenzylideneacetone)dipalladium(0) (28.5 mg, 0.031 mmol), and the mixture was stirred at 100°C for 3 hours under a nitrogen atmosphere. The mixture was concentrated and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (187 mg, 45%). ESI-MS m / z calculation for [C 26 H 22 ClN5O4S] [M+H] + :536.1;found:536.0. 1 H NMR(400 MHz,Chloroform-d)δ 8.41(d,J=2.4 Hz,1H),7.65(d,J=2.0 Hz,1H),7.43-7.41(m,2H),7.39-7.36(m,2H),7.34-7.26(m,6H),5.67(d,J=5.6 Hz,1H),5.54(s,1H),4.81(d,J=11.6 Hz,1H)4.64(d,J=11.6 Hz,1H),4.40(dd,J=10.8,5.2,1H),4.29(d,J=3.2 Hz,1H),4.07(t,J=4.0 Hz,3H),3.78(dd,J=10.8,3.2 Hz,1H).

[0291] 5-Chloro-2-cyanopyridin-3-yl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 3-azido-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-D-galactopyranoside (75 mg, 0.14 mmol) and trimethyl(2-thiazol-2-ylethynyl)silane (38 mg, 0.21 mmol) in DMF (2 mL), sodium (+)-L-ascorbate (14 mg, 0.07 mmol) and copper(II) sulfate pentahydrate (17.6 mg, 0.07 mmol) were added, and the mixture was stirred at room temperature overnight. The mixture was concentrated and purified by column chromatography (PE / EtOAc = 5 / 1 to 3 / 2, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (74.0 mg, 82%). ESI-MS m / z calculation for [C 31 H 25 ClN6O4S2] [M+H] + :645.1,found:645.1. 1 H NMR(400 MHz,DMSO-d6)δ 8.45(d,J=2.0 Hz,1H),8.23(s,1H),7.95(s,1H),7.67(d,J=2.0 Hz,1H),7.33-7.29(m,6H),7.19-7.14(m,5H),5.79(d,J=5.2 Hz,1H),5.45(s,1H),5.32(d,J=10.8 Hz,1H),4.76(q,J=11.6,5.2 Hz,1H),4.56-4.44(m,3H),4.31(s,1H),4.17(d,J=12.4 Hz,1H),4.09-4.04(m,1H).

[0292] Intermediate 6 2-Bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-(3,5-difluoro-4-(4-methoxybenzyloxy)benzyl)-1-thio-α-D-galactopyranoside [ka] To a solution of 2-bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (620 mg, 1.15 mmol) in DMF (10 mL) was added cesium carbonate (748 mg, 2.30 mmol) followed by 5-(bromomethyl)-1,3-difluoro-2-(4-methoxybenzyloxy)benzene (420 mg, 1.20 mmol), and the mixture was stirred at 25 °C for 3 h. Water (100 mL) was added, and the mixture was extracted with EtOAc (3 × 50 mL). The organic layer was washed with brine (3 × 50 mL), dried over NaSO, evaporated, and purified by column chromatography (PE / EA = 10 / 1 to 1 / 1, Silica-CS 40 g, 30 mL / min, silica gel, UV254) to give the product (700 mg, 79%). ESI-MS m / z calculation for [C 33 H 28 BrClF2N4O6S] [M+H] + :761.1;found:761.0. 1 H NMR(400 MHz,Methanol-d4)δ 8.09(d,J=2.0 Hz,1H),7.75(d,J=2.4 Hz,1H),7.49-7.41(m,2H),7.34-7.26(m,5H),6.90-6.84(m,2H),6.82-6.79(m,2H),5.96(d,J=5.2 Hz,1H),5.56(s,1H),4.99(s,2H),4.60-4.50(m,2H),4.40(dd,J=10.4,5.2 Hz,1H),4.29(d,J=3.2 Hz,1H),4.14-4.02(m,2H),3.97(s,1H),3.81(dd,J=10.4,3.2 Hz,1H),3.72(s,3H).

[0293] 5-Chloro-2-cyanopyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-(3,5-difluoro-4-(4-methoxybenzyloxy)benzyl)-1-thio-α-D-galactopyranoside [ka] To a solution of 2-bromo-5-chloropyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-(3,5-difluoro-4-(4-methoxybenzyloxy)benzyl)-1-thio-α-D-galactopyranoside (700 mg, 0.91 mmol) in DMF (10 mL) was added 1,1'-bis(diphenylphosphino)ferrocene (103 mg, 0.18 mmol), Zn (89 mg, 0.14 mol), Zn(CN) (214 mg, 1.82 mmol), and tris(dibenzylideneacetone)dipalladium(0) (105 mg, 0.18 mmol), and the mixture was stirred at 100°C for 3 hours under a nitrogen atmosphere. The mixture was evaporated and purified by column chromatography (DCM / MeOH = 10 / 0 to 10 / 1, Silica-CS 20 g, 20 mL / min, silica gel, UV254) to give the product (320 mg, 37%). ESI-MS m / z calculation for [C 34 H 28 ClF2N5O6S] [M+NH4] + :725.1,found:725.0. 1 H NMR(400 MHz,Chloroform-d)δ 8.52(d,J=2.4 Hz,1H),7.96(d,J=2.0 Hz,1H),7.52-7.48(m,2H),7.41-7.32(m,5H),7.00-6.95(m,2H),6.89-6.85(m,2H),6.00(d,J=4.8 Hz,1H),5.63(s,1H),5.08(s,2H),4.72-4.62(m,2H),4.44(dd,J=10.4,4.8 Hz,1H),4.39(d,J=3.2 Hz,1H),4.20-4.10(m,2H),3.86(dd,J=10.4,2.8 Hz,1H),3.80(s,3H),3.79-3.77(m,1H).

[0294] 5-Chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-deoxy-2-O-(3,5-difluoro-4-(4-methoxybenzyloxy)benzyl)-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-(3,5-difluoro-4-(4-methoxybenzyloxy)benzyl)-1-thio-α-D-galactopyranoside (150 mg, 0.16 mmol) in DMF (5 mL) was added trimethyl(2-thiazol-2-ylethynyl)silane (75 mg, 0.36 mmol), copper(II) sulfate pentahydrate (40.0 mg, 0.16 mmol), and sodium (+)-L-ascorbate (32 mg, 0.16 mmol), and the mixture was stirred at rt for 6 h. The mixture was partitioned between water (50 mL) and DCM (50 mL). The aqueous phase was extracted with DCM (2 × 50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over NaSO, and evaporated. The residue was purified by column chromatography (DCM / CHOH = 10 / 0 to 10 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (120 mg, 85%). ESI-MS m / z calculation for [C 39 H 31 ClF2N6O6S2] [M+H] + :817.1;found:817.1. 1 H NMR(400 MHz,Chloroform-d)δ 8.57(d,J=2.0 Hz,1H),7.98(d,J=2.4 Hz,1H),7.88(s,1H),7.52-7.40(m,7H),7.31(d,J=8.8 Hz,2H),6.87-6.82(m,2H),6.74-6.67(m,2H),6.11(d,J=5.2 Hz,1H),5.54(s,1H),5.43-5.34(m,1H),5.00(s,2H),4.95-4.88(m,1H) ,4.60-4.57(m,2H),4.49-4.40(m,2H),4.27-4.17(m,2H),3.79(s,3H).

[0295] Intermediate 7 3,5-Dichloro-4-fluorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,5-dichloro-4-fluorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (300 mg, 0.62 mmol) in DMF (10 mL) was added 4-(2-trimethylsilylethynyl)thiazol-2-ol (243 mg, 1.23 mmol), copper(II) sulfate pentahydrate (77.0 mg, 0.31 mmol), and sodium (+)-L-ascorbate (122 mg, 0.62 mmol), and the mixture was stirred at RT for 2 h. The mixture was partitioned between water (10 mL) and DCM (10 mL), and the aqueous phase was extracted with DCM (2 × 5 mL). The combined organic phase was washed with water (20 mL) and brine (20 mL), dried over NaSO, evaporated, and purified by column chromatography (PE / EA = 1 / 5 to 1 / 1, Silica-CS 12 g, 12 mL / min, silica gel, UV254) to give the product (310 mg, 82%). ESI-MS m / z calculation for [C 25 H 21 Cl2FN4O5S2] [M+H] + :611.0;found:611.0. 1 H NMR(400 MHz,Chloroform-d)δ 10.02(s,1H),8.12(s,1H),7.44(d,J=6.0 Hz,2H),7.33(s,5H),6.40(s,1H),6.15(d,J=5.1 Hz,1H),5.43(s,1H),5.23(dd,J=11.3,3.1 Hz,1H),4.53(dd,J=11.3,5.1 Hz,1H),4.42(d,J=3.0 Hz,1H),4.29(t,J=6.0 Hz,2H),4.15(d,J=12.4 Hz,1H),3.34(s,3H).

[0296] Intermediate 8 3,4-Dichlorophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 2,4,6-tri-O-acetyl-3-azido-3-deoxy-β-D-galactopyranosyl chloride (600 mg, 1.72 mmol) and 3,4-dichlorobenzenethiol (369 mg, 2.06 mmol) in DMF (10.0 mL) was added CsCO (1.1 g, 3.43 mmol), and the mixture was stirred at room temperature for 3 h. Water (30 mL) was added, and the mixture was extracted with EtOAc (2 × 20 mL). The combined organic phases were dried, concentrated, and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (550 mg, 65%). ESI-MS m / z calculation for [C 18 H 19 Cl2N3O7S] [M+NH4] + :509.0,found:509.0. 1 H NMR(400 MHz,Chloroform-d)δ 7.50(d,J=2.1 Hz,1H),7.31(d,J=8.4 Hz,1H),7.21(dd,J=8.5,2.2 Hz,1H),5.90(d,J=5.5 Hz,1H),5.40(d,J=2.7 Hz,1H),5.20(dd,J=10.9,5.5 Hz,1H),4.53(dd,J=7.0,5.4 Hz,1H),3.99(ddd,J=19.3,11.6,6.3 Hz,2H),3.87(dd,J=11.0,3.3 Hz,1H),2.12(s,3H),2.10(s,3H),1.93(s,3H)

[0297] 3,4-Dichlorophenyl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 3,4-dichlorophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (550 mg, 1.12 mmol) in MeOH (10.0 mL) and a catalytic amount of NaOMe was stirred at rt for 30 min. Acidic resin was added to adjust the pH to 6-7. The solid was removed by filtration, and the filtrate was concentrated to give the product (400 mg, 98%). ESI-MS m / z calculation for [C 12 H 13 Cl2N3O4S] [M+NH4] + :383.0,found:383.0. 1 H NMR(400 MHz,Chloroform-d)δ 7.55(d,J=2.1 Hz,1H),7.33(d,J=8.4 Hz,1H),7.27(dd,J=8.4,2.1 Hz,1H),5.63(d,J=5.4 Hz,1H),4.49-4.33(m,1H),4.20(t,J=4.4 Hz,1H),4.12(s,1H),3.87(ddd,J=33.9,12.0,4.5 Hz,2H),3.49(dd,J=10.5,2.9 Hz,1H),2.87(s,1H),2.28(d,J=7.3 Hz,1H),2.09(d,J=12.5 Hz,1H).

[0298] 3,4-Dichlorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside (400 mg, 1.09 mmol) in DMF (10 mL) was added benzaldehyde dimethyl acetal (416 mg, 2.73 mmol), followed by D(+)-10-camphorsulfonic acid (76.1 mg, 0.33 mmol). The mixture was stirred at 50 °C for 4 h with a water pump connected. The mixture was added dropwise to aqueous NaHCO (50 mL) and filtered. The white solid was collected and dried in vacuo to give the product (450 mg, 91%). ESI-MS m / z calculation for [C 19 H 17 Cl2N3O4S] [M+H] + :454.0,found:454.0. 1 H NMR(400 MHz,DMSO-d6)δ 7.74(d,J=2.1 Hz,1H),7.60(d,J=8.5 Hz,1H),7.51-7.33(m,6H),6.18(s,1H),5.97(d,J=5.2 Hz,1H),5.67(s,1H),4.42(d,J=2.9 Hz,1H),4.31(dd,J=10.9,5.2 Hz,1H),4.16-4.04(m,1H),4.01(s,1H),3.92(d,J=12.5 Hz,1H),3.65(dd,J=10.9,3.3 Hz,1H).

[0299] 3,4-Dichlorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-isopropyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (20.0 mg, 0.044 mmol) in DMF (2.0 mL) was added NaH (60% in oil, 4.1 mg, 0.18 mmol), and the mixture was stirred at 0 °C for 30 min. 2-Iodopropane (29.9 mg, 0.18 mmol) was added, and the mixture was stirred at rt overnight. The mixture was diluted with water (5 mL) and extracted with EtOAc (2 × 5 mL). The combined organic layers were concentrated and purified by preparative TLC (PE / EA = 4 / 1, silica gel, UV254) to give the product (15 mg, 69%). ESI-MS m / z calcd for [C 22 H 23 Cl2N3O4S] [M+H] + :496.1,found:496.0. 1 H NMR(400 MHz,Chloroform-d)δ 7.50(d,J=2.1 Hz,1H),7.45(dd,J=7.5,1.9 Hz,2H),7.29(dd,J=10.1,4.9 Hz,4H),7.21(dd,J=8.5,2.1 Hz,1H),5.90(d,J=5.2 Hz,1H),5.54(s,1H),4.31(dd,J=10.6,5.2 Hz,1H),4.25(d,J=3.0 Hz,1H),4.13(dd,J=12.6,1.4 Hz,1H),4.03(dd,J=15.8,3.1 Hz,2H),3.80(dt,J=12.2,6.1 Hz,1H),3.64(dd,J=10.6,3.3 Hz,1H),1.19(dd,J=14.2,6.1 Hz,6H).

[0300] Intermediate 9 3,4-Dichlorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside (150 mg, 0.33 mmol) in DMF (5 mL), NaH (60% in oil, 26 mg, 0.65 mmol) was added, followed by iodomethane (92 mg, 0.65 mmol), and the mixture was stirred at rt for 6 h. The mixture was diluted with water (100 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine (3 × 50 mL), dried over NaSO, concentrated, and purified by column chromatography (PE / EtOAc = 10 / 1 to 1 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (150 mg, 94%). ESI-MS m / z calculation for [C 20 H 19 Cl2N3O4S] [M+H] + :468.1;found:468.0. 1 H NMR(400 MHz,Chloroform-d)δ 7.52(d,J=2.0 Hz,1H),7.47-7.45(m,2H),7.33-7.29(m,5H),5.95(d,J=5.2 Hz,1H),5.55(s,1H),4.26(d,J=3.2 Hz,1H),4.19-4.15(m,2H),4.08-4.04(m,2H),3.63(dd,J=10.8,3.6 Hz,1H),3.48(s,3H).

[0301] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (150 mg, 0.30 mmol) in DMF (5 mL) was added 4-(trimethylsilyl)ethynyl)thiazol-2-ol (95 mg, 0.46 mmol), copper(II) sulfate pentahydrate (38 mg, 0.11 mmol), and sodium (+)-L-ascorbate (30 mg, 0.11 mmol), and the mixture was stirred at rt for 6 h. The mixture was partitioned between water (50 mL) and DCM (50 mL). The aqueous phase was extracted with DCM (2 × 50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over NaSO, and concentrated. The residue was purified by column chromatography (PE / EtOAc = 10 / 1 to 1 / 2, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (160 mg, 84%). ESI-MS m / z calculation for [C 25 H 22 Cl2N4O5S2] [M+H] + :593.1;found:593.0. 1 H NMR(400 MHz,DMSO-d6)δ 11.90(s,1 H),8.51(s,1H),7.86(d,J=2.0 Hz,1H),7.65(d,J=8.8 Hz,1H),7.54(dd,J=8.4,2.4 Hz,1H),7.40-7.33(m,5H),6.73(s,1H),6.60(d,J=4.8 Hz,1H),5.60(s,1H),5.17(dd,J=11.6,3.6 Hz,1H),4.59-4.54(m,2H),4.29(s,1H),4.15-3.96(m,2H),3.34(s,3H).

[0302] Intermediate 10 1,2,4,6-Tetra-O-acetyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranose [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-azido-3-deoxy-β-D-galactopyranoside (600 mg, 1.61 mmol), 4-(2-trimethylsilylethynyl)thiazol-2-ol (396 mg, 2.01 mmol), and CuI (31 mg, 0.16 mmol) in MeCN (20 mL) was added DIPEA (0.55 mL, 3.21 mmol), and the mixture was stirred at rt for 18 h. The mixture was concentrated, diluted with EtOAc, and washed with brine. The organic phase was dried, evaporated, and purified by chromatography (SiO2, EtOAc / PE) to give the product (521 mg, 65%). ESI-MS m / z calcd for [C 19 H 22 N4O 10 S] [M+H] + :499.1;found:498.9, 1 H NMR(400 MHz,Chloroform-d)δ 10.20(s,1H),7.94(s,1H),6.54(s,1H),5.90-5.80(m,2H),5.58(s,1H),5.22(d,J=12.1 Hz,1H),4.30-4.10(m,3H),2.18(s,3H),2.13(s,3H),2.06(s,3H),1.92(s,3H).

[0303] 4,6-Di-O-acetyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-D-galactal [ka] To a cooled (0 °C) solution of 1,2,4,6-tetra-O-acetyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranose (500 mg, 1.00 mmol) in DCM (15 mL) was added HBr / AcOH (1.04 mL, 6.02 mmol). The mixture was allowed to reach rt in 25 min. After stirring at rt for 6 h, the mixture was diluted with DCM and washed with saturated aqueous NaHCO3 and water. The organic phase was dried and evaporated, and the resulting residue was dissolved in MeCN (20 mL) along with NH4Cl (401 mg, 7.50 mmol). Zinc (491 mg, 7.50 mmol) was added to the mixture, and after stirring at rt for 4 days, the mixture was filtered through silica using EtOAc. The filtrate was concentrated and purified by chromatography (SiO2, EtOAc / petroleum ether) to give the product (25 mg, 7%). ESI-MS m / z calcd for [C 15 H 16 N4O6S] [M+H] + :381.1;found:381.1, 1 H NMR(400 MHz,Chloroform-d)δ 10.73(s,1H),7.95(s,1H),6.76(dd,J=6.2,2.2 Hz,1H),6.59(s,1H),5.85(m,1H),5.65(d,J=3.6 Hz,1H),4.91(d,J=6.3 Hz,1H),4.51(t,J=6.5 Hz,1H),4.22(dd,J=6.5,2.9 Hz,2H),2.11(s,3H),1.98(s,3H).

[0304] Intermediate 11 5-Bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside (180 mg, 0.36 mmol) and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (155 mg, 0.72 mmol) in DMF (4.0 mL) was added copper(II) sulfate pentahydrate (44.9 mg, 0.18 mmol) and sodium (+)-L-ascorbate (71.3 mg, 0.36 mmol), and the mixture was stirred at room temperature for 3 hours. The mixture was diluted with water (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA = 10 / 1 to 1 / 1, Silica-CS 4 g, 12 mL / min, silica gel, UV254). The resulting material was further purified by preparative SFC to give the product (28 mg, 12%). ESI-MS m / z calculation for [C 22 H 20 BrClN6O6S2] [M+H] + :643.0;found:642.9. 1 H NMR(400 MHz,Chloroform-d)δ 8.62(d,J=2.0 Hz,1H),8.20(d,J=2.0 Hz,1H),8.14(s,1H),7.06(s,1H),6.27(d,J=5.2 Hz,1H),5.55(d,J=2.0 Hz,1H),5.00(dd,J=11.2,2.8 Hz,1H),4.72(dd,J=10.8,5.2 Hz,1H),4.64(t,J=6.0 Hz,1H),3.96-4.07(m,2H),3.39(s,3H),2.00(s,3H),1.91(s,3H).

[0305] Intermediate 12 3-Bromo-2-cyanopyridin-5-yl 3-azido-4,6-di-O-acetyl-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside [ka] To a cooled (0 °C) solution of acetyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside (230 mg, 0.64 mmol) and 3-bromo-5-fluoropyridine-2-carbonitrile (154 mg, 0.76 mmol) in DMF (5.0 mL) was added diethylamine (93.1 mg, 1.27 mmol), and the mixture was stirred at 0 °C for 8 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine, dried over Na SO , concentrated, and purified by column chromatography (PE / EA = 10 / 1 to 3 / 1, Silica-CS 4 g, 12 mL / min, silica gel, UV254) to give the product (203 mg, 64%, α / β = 0.25:1). ESI-MS m / z calculation for [C 17 H 18 BrNOS] [M+H] + :500.0;found:500.0. 3-Bromo-2-cyanopyridin-5-yl 3-azido-4,6-di-O-acetyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside 1 H NMR(400 MHz,Chloroform-d)δ 8.58(d,J=2.0 Hz,1H),8.08(d,J=2.0 Hz,1H),6.07(d,J=5.6 Hz,1H),5.35(d,J=2.8 Hz,1H),4.37-4.41(m,1H),4.06-4.10(m,1H),3.90-3.95(m,1H),3.75(dd,J=10.8,3.2 Hz,1H),3.49(s,3H),3.32-3.38(m,1H),2.10(s,3H),1.90(s,3H). 3-Bromo-2-cyanopyridin-5-yl 3-azido-4,6-di-O-acetyl-3-deoxy-2-O-methyl-1-thio-β-D-galactopyranoside 1H NMR(400 MHz,Chloroform-d)δ 8.62(d,J=2.0 Hz,1H),8.08(d,J=2.0 Hz,1H),5.35(d,J=2.8 Hz,1H),4.74(d,J=9.2 Hz,1H),4.06-4.10(m,1H),3.90-3.95(m,2H),3.64(dd,J=10.8,3.2 Hz,1H),3.56(s,3H),3.32-3.38(m,1H),2.11(s,3H),2.02(s,3H).

[0306] 3-Bromo-2-cyanopyridin-5-yl 4,6-di-O-acetyl-3-deoxy-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3-bromo-2-cyanopyridin-5-yl 3-azido-4,6-diacetyl-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside (203 mg, 0.41 mmol) and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (175 mg, 0.81 mmol) in DMF (6.0 mL) was added copper(II) sulfate pentahydrate (50.7 mg, 0.20 mmol) and sodium (+)-L-ascorbate (80.4 mg, 0.41 mmol), and the mixture was stirred at room temperature for 3 hours. The mixture was diluted with water (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA = 10 / 1 to 1 / 1, Silica-CS 4 g, 12 mL / min, silica gel, UV254). The resulting material was further purified by preparative SFC to give the product (35 mg, 13%). ESI-MS m / z calculation for [C 22 H 20 BrClN6O6S2] [M+H] + :643.0;found:643.0. 1H NMR(400 MHz,Chloroform-d)δ 8.64(d,J=2.0 Hz,1H),8.13(s,1H),8.11(d,J=2.0 Hz,1H),7.07(s,1H),6.22(d,J=5.2 Hz,1H),5.54(d,J=2.4 Hz,1H),4.96(dd,J=11.2,3.2 Hz,1H),4.71(dd,J=11.2,5.2 Hz,1H),4.59-4.62(m,1H),4.01-4.06(m,2H),3.34(s,3H),2.01(s,3H),1.91(s,3H).

[0307] Intermediate 13 5-Chloro-2-cyanopyridin-3-yl 4,6-O-benzylidene-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloro-2-cyanopyridin-3-yl 3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (130 mg, 0.28 mmol) and 2-(4-chlorothiazol-2-yl)ethynyltrimethylsilane (103 mg, 0.57 mmol) in DMF (5 mL), sodium (+)-L-ascorbate (112 mg, 0.57 mmol) and copper(II) sulfate pentahydrate (35.3 mg, 0.14 mmol) were added, and the mixture was stirred at room temperature overnight. The mixture was concentrated and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (70 mg, 41%). ESI-MS m / z calculation for [C 25 H 20 Cl2N6O4S2] [M+H] + :603.0,found:603.0. 1H NMR(400 MHz,Chloroform-d)δ 8.50(d,J=2.1 Hz,1H),8.24(s,1H),8.02(d,J=2.1 Hz,1H),7.36-7.28(m,5H),7.05(s,1H),6.21(d,J=5.2 Hz,1H),5.45(s,1H),5.26(dt,J=11.2,5.6 Hz,1H),4.58-4.46(m,2H),4.32(s,1H),4.19(dd,J=12.9,1.4 Hz,1H),4.09-4.00(m,1H),3.34(s,3H).

[0308] Intermediate 14 3-Chloro-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside [ka] To a coo...

Claims

1. D-galactopyranosyl compound of formula (1) 【Chemistry 1】 (In the formula, the pyranosyl ring is α-D-galactopyranosyl; A １ teeth, 【Chemistry 2】 and 【Chemistry 3】 (wherein an asterisk ＊ represents a carbon atom of a heteroaromatic ring covalently bonded to the triazole group of formula (1); R ２ is hydrogen, C １～６ selected from the group consisting of alkyl, OH and halogen; R ３ is hydrogen, C １～６ selected from the group consisting of alkyl and halogen; R ４ is selected from the group consisting of OH, halogen and amino; R ５ is hydrogen, C １～６ selected from the group consisting of alkyl and halogen selected from the group consisting of: X is S, SO, SO ２ , O, C=O and CR ２ａ R ３ａ is selected from R ２ａ and R ３ａ is independently selected from hydrogen, OH, or a halogen; B １ is a) CN, halogen, methyl optionally substituted with F, OCH optionally substituted with F ３ , OCH optionally substituted with F ２ CH ３ , OH and R ４ａ -CONH- (wherein, R ４ａ is C １～３ C substituted with a 5- or 6-membered heteroaromatic ring optionally substituted with a substituent selected from alkyl and cyclopropyl １～６ Alkyl or branched C ３～６ alkyl; or CN, halogen, methyl optionally substituted with F, OCH optionally substituted with F ３ , OCH optionally substituted with F ２ CH ３ , OH and R ５ａ -CONH- (wherein, R ５ａ is C １～３ C substituted with phenyl optionally substituted with a substituent selected from alkyl and cyclopropyl １～６ a) alkyl; b) halogen; N-(2-oxa)-6-azaspiro[3.3]heptanyl; C ２ -alkynyl; CN; -COOH; COOC １～４ Alkyl; -CONR ６ R ７ (In the formula, R ６ and R ７ is H, C １～３ independently selected from alkyl, cyclopropyl and isopropyl, or R ６ and R ７ together with the nitrogen form a heterocycloalkyl; C optionally substituted with F １～３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; SC optionally substituted with F １～３ Alkyl; OC optionally substituted with F １～３ Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR ８ R ９ (In the formula, R ８ and R ９ is H, C １～３ alkyl and isopropyl); OH; and R １０ -CONH- (wherein, R １０ is C １～３ c) phenyl or naphthyl optionally substituted with a group selected from alkyl, cyclopropyl, aryl, and heterocycle; ２ -alkynyl, CN, methyl optionally substituted with F, OCH optionally substituted with F ３ , OCH optionally substituted with F ２ CH ３ , OH and R １１ -CONH- (wherein, R １１ is C １～３ C optionally substituted with a substituent selected from alkyl and cyclopropyl ５～７ cycloalkyl; and d) halogen; N-(2-oxa)-6-azaspiro[3.3]heptanyl; C ２ -alkynyl; CN; -COOH; COOC １～４ Alkyl; -CONR １２ R １３ (In the formula, R １２ and R １３ is H, C １～３ independently selected from alkyl, cyclopropyl and isopropyl, or R １２ and R １３ together with the nitrogen form a heterocycloalkyl; C optionally substituted with F １～３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; SC optionally substituted with F １～３ Alkyl; OC optionally substituted with F １～３ Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; SC optionally substituted with F １～３ Alkyl; NR １４ R １５ (In the formula, R １４ and R １５ is H, C １～３ alkyl and isopropyl); OH; aryl; heterocycle; and R １６ -CONH- (wherein, R １６ is C １～３ e) heteroaryl or heterocycloalkyl optionally substituted with a group selected from C １～６ Alkyl or branched C ３～６ alkyl; f) C ２～６ alkynyl; R １ is selected from the group consisting of H, OC 1-4 alkyl, and OC 1-4 alkyl substituted with at least one selected from the group consisting of phenyl substituted with one or more groups selected from phenyl, OH, and halogen; or a pharma- ceutically acceptable salt or solvate thereof.

2. A １ but 【Chemistry 4】 【Chemistry 5】 【Chemistry 6】 【Chemistry 7】 【Chemistry 8】 and 【Chemistry 9】 2. The compound of claim 1 selected from the group consisting of:

3. A １ but 【Chemistry 10】 (In the formula, R ２ is a halogen; R ３ C １～６ selected from the group consisting of alkyl and halogen 2. The compound of claim 1 ,

4. 4. The compound according to claim 1, wherein X is selected from S.

5. B1 is halogen; ２ -alkynyl; CN; methyl optionally substituted with F; spiroheterocycle; SC optionally substituted with F １～３ Alkyl; CONR １２ R １３ (In the formula, R １２ and R １３ is H, C １～３ independently selected from alkyl, cyclopropyl and isopropyl, or R １２ and R １３ (c) together with the nitrogen to form a heterocycloalkyl; and tetrahydropyridine.

6. B1 is Cl; Br; F; ethynyl; N-(2-oxa)-6-azaspiro[3.3]heptanyl; CO-azetidinyl; CONHCH ３ ;CONHC ２ CH ３ ;CON(CH ３ ) ２ ;CN;Methyl;SCH ３ ; SCF ３ ;CF ３ 6. The compound of claim 5, wherein the pyridinyl is optionally substituted with a group selected from: imidazole; pyridine; pyrimidine; oxazole; and thiazole.

7. B1 is Cl; Br; F; ethynyl; N-(2-oxa)-6-azaspiro[3.3]heptanyl; CO-azetidinyl; CONHCH ３ ;CONHC ２ CH ３ ;CON(CH ３ ) ２ ;CN;Methyl;SCH ３ ; SCF ３ ;CF ３ 6. The compound of claim 5, wherein the benzothiazolyl or thiazolylpyridyl is optionally substituted with a group selected from: imidazole; pyridine; pyrimidine; oxazole; and thiazole.

8. 8. The compound according to any one of claims 1 to 7, wherein B1 is selected from tetrahydrobipyridines.

9. B1 is halogen; CN; -CONR ６ R ７ (In the formula, R ６ and R ７ is H, C １～３ alkyl, cyclopropyl, and isopropyl; and C optionally substituted with F. １～３ 8. A compound according to any one of claims 1 to 7, selected from phenyl optionally substituted with a group selected from alkyl.

10. B1 is Cl; F; Br; CN; CONHCH ３ and C optionally substituted with F １～３ 8. A compound according to any one of claims 1 to 7, selected from phenyl optionally substituted with a group selected from alkyl.

11. R １ A compound according to any one of claims 1 to 10, wherein is selected from O-methyl, O-ethyl or O-isopropyl.

12. 3,5-dichloro-4-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 2-O-benzyl-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-bromo-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-2-cyanopyridin-5-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-chlorothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyrimidin-5-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(thiazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-4-(trifluoromethyl)phenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-deoxy-3-[4-(4-methyltriazol-2-yl)-1H-1,2,3-thiazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-methylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptanyl}pyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,5-dichloro-4-fluorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside, 3-cyano-2-(trifluoromethyl)pyridin-5-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-azetidinylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4,5-dichlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-(N-methylcarbonyl)phenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanophenyl 3-[4-(5-chloro-4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 2,5-dichlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-chlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-fluorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-fluorophenyl 3-deoxy-3-[4-(4-methylthiazol-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-2-O-ethyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-deoxy-2-O-(2,2,2-trifluoroethyl)-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyanopyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 3-chloro-4-cyanophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-(N,N-dimethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 5-ethynyl-2-(N,N-dimethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynyl-2-(N-azetidinylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-ethylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-(N-methylcarbamoyl)-3-pyridinyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside, 1,3-benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 1,3-benzothiazol-6-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 1,3-benzothiazol-6-yl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-cyano-1,3-benzothiazol-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, Thiazolo[4,5-b]pyridin-6-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-Methylsulfanylpyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, and 5-(trifluoromethylsulfanyl)pyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside 2. The compound of claim 1 selected from the group consisting of: or a pharma- ceutically acceptable salt or solvate thereof.

13. A pharmaceutical comprising a compound according to any one of claims 1 to 12.

14. 13. A pharmaceutical composition comprising a compound according to any one of claims 1 to 12, and optionally a pharma- ceutically acceptable excipient.

15. A pharmaceutical composition comprising a compound according to any one of claims 1 to 12 for the treatment of disorders associated with the binding of Galectin-1 and / or Galectin-3 to their ligands in a mammal, said disorders being inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndromes; pulmonary, hepatic, renal, ocular and cutaneous and cardiac fibrosis; Dupuytren's and Peyronie's diseases; coronary artery stents, biliary stents, cerebral artery stents, ureteral stents, and the like. Fibrotic complications of stents; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonia; abnormal scar formation; surgical adhesions; septic shock; colorectal cancer, pancreatic cancer, gastric cancer, biliary tract cancer, lung cancer, mesothelioma, breast cancer, ovarian cancer, uterine cancer, cervical cancer, salpingx cancer, medulloblastoma, glioma, meningioma, sarcoma of bone and muscle and other sarcomas, leukemia and T-cell lymphoma; Transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven osteogenesis imperfecta; pulmonary hypertension; psoriasis, rheumatoid arthritis, rheumatoid lung; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; influenza virus, HIV, herpes virus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; ocular angiogenesis or diseases or conditions associated with ocular angiogenesis, neovascularization associated with cancer; and age-related macular degeneration and corneal neovascularization. A pharmaceutical composition selected from the group consisting of angiogenesis; atherosclerosis; metabolic diseases; diabetes; type I diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Loeys-Dietz syndrome; nephropathy; diastolic HF; fibrotic pulmonary complications of aPD1 and other CPI treatment; asthma and other interstitial lung diseases (including Hermansky-Pudlak syndrome), non-alcoholic steatohepatitis or non-alcoholic fatty liver disease; uterine fibroids and uterine or cervical fibrosis.

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