Novel galactoside inhibitors of galectins

Abstract

This invention relates to a D-galactopyranose compound of formula (1), wherein the pyranose ring is α-D-galactopyranose, and these compounds are high-affinity galactolectin-1 and / or galactolectin-3 inhibitors for 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; liver disorders.

Description

Technical Field

[0001] This invention relates to novel compounds, the use of said compounds as pharmaceutical agents, and the use of agents for treating cancer in mammals; fibrosis; scarring; keloid formation; abnormal scar formation; surgical adhesions; pathological angiogenesis; eye diseases; HIV-1 disease; inflammation; or transplant rejection. The invention also relates to pharmaceutical compositions comprising said novel compounds. Background Technology

[0002] Galactolectins are proteins with a characteristic 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 defining characteristics: 1) a β-galactose binding site, and 2) sufficient similarity in a sequence motif of approximately seven amino acids, most of which (approximately six residues) constitute the β-galactose binding site. However, tight binding to natural sugars requires sites adjacent to the β-galactose site, and different biases of these sites confer varying fine specificities to natural sugars on galactolectins.

[0003] Recent completed human, mouse, and rat genome sequences have revealed approximately 15 galactoglucosinolates and galactoglucosinolate-like proteins in a mammalian genome, with subtle differences between species (Leffler et al., 2004).

[0004] Galactolectin subunits can contain one or two CRDs within a single polypeptide chain. The first class, mono-CRD galactolectins, can occur in vertebrates as monomers or dimers (both types). The best-studied galactolectins to date are the dimer galactolectin-1 and galactolectin-3, which are monomers in solution but can aggregate and become polymers upon encountering ligands (Lepur et al., 2012). These were the first galactolectins discovered and are abundant in many tissues.

[0005] There are currently over 5,700 publications on galactogranins in PubMed, and as mentioned above, the majority are on galactogranin-1 (>1,400) and galactogranin-3 (>2,800). Strong evidence supports the role of galactogranins in, for example, inflammation and cancer, as well as in development (Blidner et al., 2015; Ebrahim et al., 2014).

[0006] Galactolectins are synthesized as cytosol proteins and lack a signal peptide on free ribosomes. Their N-terminus is acetylated (a typical modification for cytosol proteins), and they remain in the cytosol for extended periods (not a typical characteristic of secretory proteins). They can target the nucleus, specific cytosol sites, or be secreted (inducibly or constitutively) via non-canonical (non-ER-Golgi) pathways (as first demonstrated with galactolectin-1 (Cooper and Barondes, 1991)), the mechanisms of which are not yet known but may be similar to, for example, the derivation of IL-1 (Leffler et al., 2004; Arthur et al., 2015). Galactolectins can function in all of these compartments; for galactolectin-1, strong evidence published in prestigious journals supports its role in nuclear RNA splicing, H-RAS activation in the cytosol, accumulation around ruptured vesicles, and various extracellular actions related to cell signaling and adhesion (Elola et al., 2015; Aits et al., 2015; Blanchard et al., 2016). Other galactolectins may also function in the cytosol by enhancing apoptosis and regulating the cell cycle and differentiation in certain cells. Most galactolectins also function extracellularly by cross-linking glycoproteins (e.g., laminin, integrin, and IgE receptors), potentially forming supramolecular ordered arrays (Elola et al., 2015), and thereby modulating cell adhesion and inducing intracellular signaling. Relatedly, molecular mechanisms underlying these galactolectin functions have been observed in recent years, involving the formation of microdomains (lattices) within the membrane (Elola et al., 2015), which in turn affects intracellular transport and cell surface presentation of glycoprotein receptors. This has been documented in cell cultures treated with galactolectin or galactolectin inhibitors, as well as in null mutant mice and animals.

[0007] Galactochonin-1, the first discovered and second most studied galactochondrin, is expressed with some bias in all tissues, but not excluding mesenchymal-derived cells such as fibroblasts and lymphocytes. It is involved in regulating cell growth, adhesion, signal transduction, differentiation, development, the immune system, and host-pathogen interactions (Blanchard et al., 2016). The expression profile of galactochonin-1 at various stages of cancer progression and its role in the tumor microenvironment have been thoroughly reviewed.

[0008] Galactochondrin-1 is associated with a wide variety of phenomena, and therefore, its inhibitors can have multiple uses. This could easily be dismissed as a lack of specificity or scientific focus. Therefore, an analogy with aspirin and cyclooxygenases (COX-I and II) is useful. COX produces precursors to many prostaglandins and is thus involved in a wide variety of biological mechanisms. Its inhibitors, aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs), also have broad and diverse effects. Nevertheless, these inhibitors are very useful in medicine, and they possess several distinct specific uses.

[0009] Therefore, if lectins, like COX, are part of some fundamental biological regulatory mechanism (which is currently unknown), they are likely to be "used by nature" for different purposes in different contexts. Galectin inhibitors, such as NSAIDs, are not expected to eliminate the entire system, but rather to slightly tilt the balance.

[0010] Galactoglobulin-1 in immunity and inflammation

[0011] Galactolectin-1 has been found to primarily possess immunosuppressive and anti-inflammatory effects (Elola et al., 2015), although it may also be pro-inflammatory in some cases. Galactolectin-1 binds to specific glycosylation patterns on T helper cells to selectively induce apoptosis in activated Th1 and Th17 cells (Perillo et al., 1995) (Toscano, MA et al., 2007). The immunosuppressive effects of galactolectin-1 have suggested that galactolectin-1 itself may be a potential treatment for autoimmune diseases and other inflammatory conditions. Conversely, inhibiting its immunosuppressive effects in, for example, cancer has also been proposed as a therapeutic approach, as described below.

[0012] Galactochondrin-1 in angiogenesis

[0013] Like galactolectin-3, galactolectin-1 has been shown to promote angiogenesis in certain circumstances in a manner involving its carbohydrate-binding activity (Hockl et al., 2016). Of particular interest is the observation that it may promote tumor angiogenesis through a pathway parallel to VEGF. Therefore, inhibition of galactolectin-1 may be anti-angiogenic when anti-VEGF-based inhibition fails. The discovery of the binding of the anti-angiogenic peptide Anginex (and related compounds) to galactolectin-1 suggests another mechanism by which galactolectin-1 plays a role in angiogenesis, but the details remain unclear; Anginex has been described in some reports as inhibiting galactolectin-1 activity, but in others as enhancing its carbohydrate-binding activity.

[0014] Galactoglobulin-1 in fibrosis-related diseases

[0015] The idea of ​​a potential role for galectin-3 in fibrosis stems from cellular and in vitro studies of macrophage differentiation (Mackinnon et al., 2008) and in vivo studies of macrophage differentiation and myofibroblast activation (Mackinnon et al., 2012). In short, the hypothesis is that galectin-3 has been shown to prolong cell surface residence time and thus enhance TGF-β receptor responsiveness (Partridge et al., 2004), which in turn regulates alternative macrophage differentiation into M2 macrophages and myofibroblast activation. Galectin-1 has also been shown to play a role in fibrosis, including through TGF-β-related mechanisms, but the evidence is less clear than that for galectin-3.

[0016] Therefore, galactolectin-1 is also a good candidate as an endogenous enhancer of TGF-β signaling and myofibroblast activation (Kathiriya et al.), and galactolectin-1 inhibitors may also be used to treat fibrosis and poor tissue remodeling.

[0017] Galactoglobulin-1 in cancer

[0018] Numerous immunohistochemical studies have shown that the expression of certain galactoglucosins is altered in cancer (vanden Brule et al. and Bidon et al., Leffler (ed.), 2004b), and, for example, galactoglucosin-3 is now a recognized histochemical marker for thyroid cancer. Direct evidence for the role of galactoglucosin-3 in cancer comes from mouse models, primarily through Raz et al., but also from others (Leffler (ed.), 2004b). In paired tumor cell lines (with decreased or increased expression of galactoglucosin-3), galactoglucosin-3 induction produces more tumors and metastases, while inhibition of galactoglucosin-3 produces fewer tumors and metastases. It has been proposed that galactoglucosin-3 enhances tumor growth through anti-apoptosis, promotes angiogenesis, or promotes metastasis by affecting cell adhesion. Furthermore, recent evidence suggests that galactoglucosin-3 plays a crucial role in the tumor microenvironment – ​​reviewed in (Ruvolo, 2015). It is also believed that galectin-3 modulates the interaction 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). It is clear from the above that galectin-3 inhibitors may have valuable anticancer effects. Indeed, sugars that inhibit galectin-3 have been reported to have anticancer effects, though not confirmed. In our own study, the CRD-containing fragment of galectin-3 inhibited breast cancer in a mouse model by acting as a dominant-negative inhibitor (John et al., 2003). Recently, it has been demonstrated that inhibition of galectin-3 with small molecules significantly enhances the sensitivity of tumor cells to radiation and standard pro-apoptotic drugs in cellular assays and in vitro (Lin et al., 2009) and in vivo (Glinsky et al., 2009).

[0019] Furthermore, galectin-1 is typically overexpressed in poorly differentiated cancer cells, and galectin-9 or its analogues galectin-4 and galectin-8 may be induced in certain cancer types (Huflejt and Leffler, 2004; Leffler (ed.), 2004b). Galectin-1 induces apoptosis in activated T cells and exhibits remarkable immunosuppressive effects in vivo against autoimmune diseases (Rabinovich et al.; and Pace et al., Leffler (ed.), 2004b). Therefore, overexpression of these galectins in cancer may help tumors defend themselves against host-induced T cell responses.

[0020] Null mutant mice of galectin-1 and galectin-3 were established several years ago (Poirier, 2002). They are healthy and reproduce normally under animal housing conditions. However, recent studies have revealed subtle phenotypes in galectin-3 null mutants regarding neutrophil and macrophage function (as described above) and bone formation, and in galectin-1 null mutants regarding nerve and muscle cell regeneration / differentiation (Leffler et al., 2004; Poirier, 2002; Watt, Leffler (ed.), 2004b). Recently, null mutant mice of galectin-7 and galectin-9 have been generated and are also perfectly healthy under animal housing conditions, but detailed analysis has not yet been performed. Differences in expression sites, specificity, and other characteristics make it unlikely that the different galectins are functionally interchangeable. Observations in null mutant mice suggest that galactolectins are not essential for basic life-support functions, as can be observed under normal animal housing conditions. Instead, they may be optimizers of normal function and / or essential in stress conditions not found in housing conditions. The lack of potent effects in null mutant mice may make galactolectin inhibitors more attractive as drugs. Inhibition of galactolectin if its activity contributes to the pathological conditions described above but contributes less to normal conditions would likely have fewer undesirable side effects.

[0021] Therefore, drugs targeting galactoglobulin-1 activity in cancer (such as those that suppress immunity or enhance angiogenesis) may become useful anti-cancer treatments.

[0022] Known inhibitors

[0023] Natural ligands

[0024] Solid-binding and inhibition assays have identified many sugars and glycoconjugates capable of binding galactolectins (reviewed in Leffler, 2001; Leffler et al., 2004). All galactolectins bind at approximately 0.1–1 mM K. d Lactose binding affinity. D-galactose has an affinity that is 1 / 50th to 1 / 100th that of lactose. N-acetyllactose and related disaccharides have similar binding affinity to lactose, but for some galactogranins, their binding affinity may be weaker or up to 10 times better. Both galactose (10 mM) (Tejler et al. 2009) and lactose (190 μM) (van Hattum, 2013) have low affinity for galactogranin-1.

[0025] The aforementioned natural sugars, which have been identified as galactolectin-1 ligands, are unsuitable for use as active ingredients in pharmaceutical compositions because they are susceptible to acidic hydrolysis and enzymatic degradation in the stomach. Furthermore, natural sugars are inherently hydrophilic and poorly absorbed from the gastrointestinal tract after oral administration.

[0026] Galactose lectin specificity

[0027] Studies using galactogranin-specific inhibition by the aforementioned small natural sugars have shown that all galactogranins bind to lactose, LacNAc, and related disaccharides, but galactogranin-3 binds better to certain longer sugars (Leffler and Barondes, 1986). These longer sugars are characterized by additional sugar residues added at the C-3 position of galactose (in, for example, lactose or LacNAc), which bind to an extended binding groove. The shape of this groove varies with the galactogranin, indicating that the same extension will not be bound equally by different galactogranins.

[0028] Synthesis inhibitors

[0029] A recent patent review covering galectin-1 inhibitors and their potential as therapeutic agents was published (Blanchard 2016). The small monosaccharides covered in this review have been reported to have an affinity for galectin-1, at best similar to lactose. On the other hand, disaccharides, particularly dithiogalactoside (TDG), have been reported to have high affinity for galectin-1 (T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285).

[0030] Amino acid-coupled sugars with anticancer activity were first identified as natural compounds in serum, but synthetic analogs were subsequently created (Glinsky et al., 1996). Among these, those conjugated with amino acids, such as lactose or galactose, inhibit galactogranin, but with roughly the same potency as the corresponding underived sugars. Dihydroporphyrin-coupled lactose has been reported to have high affinity (0.54 μM), as measured in an ELISA assay (Pandey et al., 2002, EP 1256586(A1)). Chemically modified forms of citrus pectin that inhibit galactogranin-3 (Platt and Raz, 1992) have shown antitumor activity in vivo (Pienta et al., 1995; Nanga-Makker et al., 2002). Cluster molecules with up to four lactose moieties exhibit a strong multivalent effect when bound to galectin-3, but not when bound to galectin-1 and galectin-5 (Vrasidas et al., 2003). Cyclodextrin-based sugar clusters with seven galactose, lactose, or N-acetyllactose residues also show a strong multivalent effect on galectin-3, but a weaker effect on galectin-1 and galectin-7 (André et al., 2004). Starburst dendritic polymers (André et al., 1999) and glycopolymers (Pohl et al., 1999; David et al., 2004) (becoming multivalent in lactose residues) have been described as galectin-3 inhibitors with slightly increased potency compared to lactose. Multivalent lactose derivatives have been shown to have a significant cluster effect on galectin-1 (Tejler et al., 2006). Furthermore, these compounds exhibit selectivity relative to other galactolectins. Peptide-based compounds (such as Anginex) and non-peptide topological mimics (Dings et al., 2012) have been reported as allosteric galactolectin-1 inhibitors. The aforementioned synthetic compounds, identified as galactolectin-1 ligands, are unsuitable for use as active ingredients in pharmaceutical compositions because they are inherently hydrophilic and poorly absorbed from the gastrointestinal tract after oral administration. Additionally, these compounds exhibit moderate affinity and selectivity.

[0031] The aforementioned natural oligosaccharides, glycoclusters, glycodendromers, peptides, non-peptide topological mimics, and glycopolymers are too polar and too large to be absorbed, and in some cases large enough to trigger an immune response in patients. Furthermore, they are susceptible to acidic and enzymatic hydrolysis in the stomach. Therefore, small synthetic molecules are needed.

[0032] Thio-digalactoside is known to be a synthetic, hydrolyzed, and polar inhibitor, roughly as effective as N-acetylglucosamine (Leffler and Barondes, 1986). N-acetylglucosamine derivatives with an aromatic amide or substituted benzyl ether at C-3' have been shown to be highly effective inhibitors of galactolectin-3, with IC50 values ​​of [missing information]. 50 The value was unprecedentedly low at 4.8 μM, a 20-fold increase compared to natural N-acetyllactobiose. et al., 2002; These derivatives are generally less polar due to the presence of the aromatic amide moiety, and are therefore more suitable as agents for inhibiting galactolectins in vivo. Furthermore, C3-triazolylgalactoside has been shown to be as potent inhibitors of certain galactolectins as the corresponding C3-amides. Therefore, any structurally appropriate galactose C3-substituent can confer enhanced affinity for galactolectins.

[0033] However, due to the presence of glycosidic bonds in the sugar moieties of galactose and N-acetyllactose, compounds derived from C3-amide and C3-triazolyl groups remain susceptible to hydrolytic degradation in vivo, and even further improved affinity and stability are desirable, despite their being small molecule inhibitors of galactoglucoside-3. Therefore, inhibitors based on the 3,3'-diamidyl or 3,3'-ditriazole derivatives of thio-diagalactoside have been developed (Cumpstey et al., 2005b; Cumpstey et al., 2008; Salameh et al., 2010; WO / 2005 / 113569 and US2007185041; WO / 2005 / 113568, US 7,638,623 B2; T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285), lacking the O-glycoside hydrolytic and enzymatically unstable bonds. These inhibitors also exhibit superior affinity for several galactoglucosinolates (down to Kd in the low nM range). However, despite exhibiting high affinity for galactolectins, 3,3'-derived thiogalactosides still suffer from drawbacks in their multi-step synthesis, which involves a double inversion reaction to achieve the 3-N-derived galactose structural unit. Furthermore, cyclohexane substitution for one of the galactose rings in thiogalactosides has been shown to mimic the galactose ring and thus provide inhibitors of galactolectin-1 and galactolectin-3 with efficiencies approaching those of diamido- and ditriazolyl-thiogalactoside derivatives (WO / 2010 / 126435). Substituting the D-pyranogalactose unit with substituted cyclohexane reduces polarity and most likely also decreases metabolic susceptibility, thereby improving drug properties.

[0034] Some of the earlier described compounds have the following general formula

[0035]

[0036] As described in WO / 2005 / 113568,

[0037] and

[0038]

[0039] As described in WO / 2005 / 113569, where R I It could be D-galactose.

[0040] It was published recently (T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285).

[0041]

[0042] TDG substituted with thiophene triazole substituents at C3 and C3' positions exhibits high affinity (<10 nM) for galactogranin-1.

[0043] A compound is disclosed in the recently published US20140099319, WO2014067986, and T. Delaine, 2016, ChemBioChem10.1002 / cbic.201600285.

[0044]

[0045] It has fluorine (F) at the meta positions on the two benzene rings relative to the triazole ring. This compound has been shown to be a promising drug candidate for pulmonary fibrosis, and in particular exhibits very high selectivity and affinity for galactolectin-3.

[0046] A series of small C1 or C1 and C3 substituted galactopyranosides have been disclosed, exhibiting affinity for galactagglomerin-3 and galactagglomerin-1. β-D-galactopyranosides have reportedly possess affinity in the same range as or less than that for lactose, with a Kd of approximately 91 μM for galactagglomerin-3 and approximately 190 μM for galactagglomerin-1 (Giguere, D et al. 2011, 2008, 2006).

[0047]

[0048] There are no publicly disclosed or mentioned α-anomeric derivatives of galactogluconin-1 or galactogluconin-3 that have a better affinity for lactose. Summary of the Invention

[0049] The compounds of this invention are novel α-D-galactopyranose compounds that unexpectedly exhibit high affinity for galactogranin-1, and some compounds also show high affinity for galactogranin-3 and are considered novel and potent drug candidates. Some compounds have shown good systemic absorption in in vitro and in vivo ADME studies and are suitable for oral treatment of the diseases and disorders disclosed herein.

[0050] In a broad sense, the present invention relates to a D-galactopyranose compound of formula (1).

[0051]

[0052] in

[0053] The pyranose ring is α-D-galactopyranose.

[0054] A 1 Choose from the following groups:

[0055]

[0056] The asterisk * indicates the carbon atom of the heteroaromatic ring covalently connected to the triazole group of formula (1);

[0057] Where R 2 Choose from the following groups: hydrogen, C 1-6 Alkyl groups, OH groups, and halogens;

[0058] R 3 Choose from the following groups: hydrogen, C 1-6 Alkyl and halogen;

[0059] R 4 Choose from the following groups: OH, halogens, and amino groups;

[0060] R 5 Choose from the following groups: hydrogen, C 1-6 Alkyl and halogen;

[0061] X is selected from S, SO, SO2, O, C=O and CR 2a R 3a , where R 2a and R 3a Independently selected from hydrogen, OH, or halogen;

[0062] B 1 Selected from a) C-rings substituted with penta- or hexa-membered heterocyclic aromatic rings 1-6Alkyl or branched C 3-6 The alkyl group, wherein the five- or six-membered heteroaromatic ring is optionally substituted with a substituent selected from: CN, halogen, methyl group optionally substituted with F, OCH3 group optionally substituted with F, OCH2CH3 group optionally substituted with F, OH, and R. 4a -CONH-, where R 4a Selected from C 1-3 Alkyl and cyclopropyl; or C substituted with phenyl 1-6 Alkyl group, optionally substituted with a substituent selected from: CN, halogen, methyl group optionally substituted with F, OCH3 group optionally substituted with F, OCH2CH3 group optionally substituted with F, OH, and R. 5a -CONH-, where R 5a Selected from C 1-3 Alkyl and cyclopropyl; b) aryl, such as phenyl or naphthyl, which is optionally substituted with a group selected from: halogen; spiroheterocyclic, such as N-(2-oxa)-6-azaspiro[3.3]heptyl; C2-ynyl; C2-ynyl; CN; -COOH; COOC 1-4 Alkyl; -CONR 6 R 7 , where R 6 and R 7 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl, or R 6 and R 7 Together with the nitrogen, a heterocyclic alkyl group is formed; C, optionally substituted with F, forms a heterocyclic alkyl group. 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 , where R 8 and R 9 Independently selected from H and C 1-3 Alkyl and isopropyl; OH; and R 10 -CONH-, where R 10 Selected from C 1-3 Alkyl and cyclopropyl; aryl; and heterocyclic, c)C 5-7 Cycloalkyl, optionally substituted with a substituent selected from: halogen, C2-ynyl, CN, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 11 -CONH-, where R 11 Selected from C 1-3Alkyl and cyclopropyl; and d) heterocycles, such as heteroaryl or heterocyclic alkyl, which are optionally substituted with groups selected from: halogens; spiroheterocycles, such as N-(2-oxa)-6-azaspiro[3.3]heptyl; C2-alkynyl; CN; -COOH; COOC 1-4 Alkyl; -CONR 12 R 13 , where R 12 and R 13 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 Together with the nitrogen, a heterocyclic alkyl group is formed; C, optionally substituted with F, forms a heterocyclic alkyl group. 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 , where R 14 and R 15 Independently selected from H and C 1-3 Alkyl and isopropyl; OH; aryl; heterocyclic; and R 16 -CONH-, where R 16 Selected from C 1-3 Alkyl and cyclopropyl; e)C 1-6 Alkyl or branched C 3-6 Alkyl; f)C 2-6 acetylin

[0063] R 1 Choose from the following groups: a) H, b) OH, c) OC 1-6 Alkyl groups, optionally substituted with one or more halogens, phenyl groups, phenyl groups substituted with one or more groups selected from OH and halogens, CN, OR 17 NR 18 R 19 , and CONH2, where R 17 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 20 -CONH-, where R 20 Selected from C 1-3 Alkyl and cyclopropyl, R 18Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 21 -CONH-, where R 21 Selected from C 1-3 Alkyl and cyclopropyl, and R 19 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 22 -CONH-, where R 22 Selected from C 1-3 Alkyl and cyclopropyl, d) branched OC 3-6 Alkyl groups, optionally substituted with one or more halogens, CN, OR 23 NR 24 R 25 , and CONH2, where R 23 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 26 -CONH-, where R 26 Selected from C 1-3 Alkyl and cyclopropyl, R 24 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 27 -CONH-, where R 27 Selected from C 1-3 Alkyl and cyclopropyl, and R 25 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 28 -CONH-, where R 28 Selected from C 1-3 Alkyl and cyclopropyl, and e) cyclic OC 3-6 Alkyl groups, optionally substituted with one or more halogens, CN, OR 29 NR 30 R 31 , and CONH2, where R 29 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 32 -CONH-, where R 32 Selected from C 1-3Alkyl and cyclopropyl, R 30 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 33 -CONH-, where R 33 Selected from C 1-3 Alkyl and cyclopropyl, and R 31 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 34 -CONH-, where R 34 Selected from C 1-3 Alkyl and cyclopropyl; or

[0064] Its pharmaceutically acceptable salts or solvates.

[0065] In another aspect, the present invention relates to a D-galactopyranose compound of formula (1).

[0066]

[0067] in

[0068] The pyranose ring is α-D-galactopyranose.

[0069] A 1 Choose from the following groups:

[0070]

[0071] The asterisk * indicates the carbon atom of the heteroaromatic ring covalently connected to the triazole group of formula (1);

[0072] Where R 2 Choose from the following groups: hydrogen, C 1-6 Alkyl groups, OH groups, and halogens;

[0073] R 3 Choose from the following groups: hydrogen, C 1-6 Alkyl and halogen;

[0074] R 4 Choose from the following groups: OH, halogens, and amino groups;

[0075] R 5 Choose from the following groups: hydrogen, C 1-6 Alkyl and halogen;

[0076] X is selected from S, SO, SO2, O, C=O and CR 2a R 3a , where R 2aand R 3a Independently selected from hydrogen, OH, or halogen;

[0077] B 1 Selected from a) C-rings substituted with penta- or hexa-membered heterocyclic aromatic rings 1-6 Alkyl or branched C 3-6 The alkyl group, wherein the five- or six-membered heteroaromatic ring is optionally substituted with a substituent selected from: CN, halogen, methyl group optionally substituted with F, OCH3 group optionally substituted with F, OCH2CH3 group optionally substituted with F, OH, and R. 4a -CONH-, where R 4a Selected from C 1-3 Alkyl and cyclopropyl; or C substituted with phenyl 1-6 Alkyl group, optionally substituted with a substituent selected from: CN, halogen, methyl group optionally substituted with F, OCH3 group optionally substituted with F, OCH2CH3 group optionally substituted with F, OH, and R. 5a -CONH-, where R 5a Selected from C 1-3 a) Alkyl and cyclopropyl; b) Aryl, such as phenyl or naphthyl, which is optionally substituted with a group selected from: halogen; CN; -COOH; -CONR 6 R 7 , where R 6 and R 7 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl, or R 6 and R 7 Together with the nitrogen, a heterocyclic alkyl group is formed; C, optionally substituted with F, forms a heterocyclic alkyl group. 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 8 R 9 , where R 8 and R 9 Independently selected from H and C 1-3 Alkyl and isopropyl; OH; heterocycles; and R 10 -CONH-, where R 10 Selected from C 1-3 Alkyl and cyclopropyl; c)C 5-7 Cycloalkyl, optionally substituted with a substituent selected from: halogen, C2-ynyl, CN, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 11 -CONH-, where R 11 Selected from C 1-3Alkyl and cyclopropyl; and d) heterocycles, such as heteroaryl or heterocyclic alkyl, which are optionally substituted with groups selected from: halogens; spiroheterocycles, such as N-(2-oxa)-6-azaspiro[3.3]heptyl; C2-alkynyl; CN; -COOH; -CONR 12 R 13 , where R 12 and R 13 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 Together with the nitrogen, a heterocyclic alkyl group is formed; C, optionally substituted with F, forms a heterocyclic alkyl group. 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 , where R 14 and R 15 Independently selected from H and C 1-3 Alkyl and isopropyl; OH; heterocycles; and R 16 -CONH-, where R 16 Selected from C 1-3 Alkyl and cyclopropyl; e)C 1-6 Alkyl or branched C 3-6 Alkyl; f)C 2-6 alkynyl group,

[0078] R 1 Choose from the following groups: a) H, b) OH, c) OC 1-6 Alkyl groups, optionally substituted with one or more halogens, phenyl groups, phenyl groups substituted with one or more groups selected from OH and halogens, CN, OR 17 NR 18 R 19 , and CONH2, where R 17 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 20 -CONH-, where R 20 Selected from C 1-3 Alkyl and cyclopropyl, R 18 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 21 -CONH-, where R 21 Selected from C 1-3 Alkyl and cyclopropyl, and R19 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 22 -CONH-, where R 22 Selected from C 1-3 Alkyl and cyclopropyl, d) branched OC 3-6 Alkyl groups, optionally substituted with one or more halogens, CN, OR 23 NR 24 R 25 , and CONH2, where R 23 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 26 -CONH-, where R 26 Selected from C 1-3 Alkyl and cyclopropyl, R 24 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 27 -CONH-, where R 27 Selected from C 1-3 Alkyl and cyclopropyl, and R 25 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 28 -CONH-, where R 28 Selected from C 1-3 Alkyl and cyclopropyl, and e) cyclic OC 3-6 Alkyl groups, optionally substituted with one or more halogens, CN, OR 29 NR 30 R 31 , and CONH2, where R 29 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 32 -CONH-, where R 32 Selected from C 1-3 Alkyl and cyclopropyl, R 30 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 33 -CONH-, where R 33 Selected from C1-3 Alkyl and cyclopropyl, and R 31 Choose from the group consisting of: H, CN, halogens, methyl groups optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R. 34 -CONH-, where R 34 Selected from C 1-3 Alkyl and cyclopropyl; or

[0079] Its pharmaceutically acceptable salts or solvates.

[0080] In one implementation, B 1 Selected from d) heterocycles, such as heteroaryl or heterocyclic alkyl groups, which are optionally substituted with groups selected from: halogens; spiroheterocycles, such as N-(2-oxa)-6-azaspiro[3.3]heptyl; C2-alkynyl; CN; -COOH; -CONR 12 R 13 , where R 12 and R 13 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl; C-terminals 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 , where R 14 and R 15 Independently selected from H and C 1-3 Alkyl and isopropyl; OH; heterocycles; and R 16 -CONH-, where R 16 Selected from C 1-3 Alkyl and cyclopropyl.

[0081] In one implementation, A 1 Selected from Equation 2, where R 2 Choose from the following groups: hydrogen, methyl, OH, and halogen; and R 3 Choose from the following groups: hydrogen, C 1-6 Alkyl groups and halogens. In a preferred embodiment, R 2 It is hydrogen, methyl, or halogen, and R 3 It is H. Depending on conditions such as acidity or alkalinity, the OH group can be in the form of an oxotautomer. In another preferred embodiment, R 2 It is halogen, and R 3 It is hydrogen. In yet another implementation, R 2 It is a halogen, such as Cl; and R3 Choose from the following groups: C 1-6 Alkyl groups, such as methyl groups; and halogens, such as Cl.

[0082] In yet another implementation plan, A 1 Selected from Equation 3, where R 4 Choose from the following groups: OH, halogens, and amino groups; and R 5 Choose from the following groups: hydrogen, C 1-6 Alkyl groups and halogens. In a preferred embodiment, R 4 It is OH and R 5 It is hydrogen. In another preferred embodiment, R 4 It is an amino group and R 5 It is hydrogen. In yet another preferred embodiment, R 4 It is halogen and R 5 It is hydrogen.

[0083] In a preferred embodiment, A 1 yes

[0084]

[0085] In yet another implementation plan, A 1 yes

[0086]

[0087] In another preferred embodiment, A 1 yes

[0088] and

[0089] R 1 Choose from the following groups: a), c), d), and e) of the above aspects.

[0090] In yet another preferred embodiment, A 1 yes

[0091]

[0092] In yet another preferred embodiment, A 1 yes

[0093] and

[0094] R 1 Choose from the following groups: a), c), d), and e) of the above aspects.

[0095] In yet another preferred embodiment, A 1 yes

[0096] and

[0097] R 1 Choose from the following groups: a), c), d), and e) of the above aspects.

[0098] In yet another implementation plan, A 1 yes

[0099]

[0100] In yet another implementation plan, A 1 yes

[0101]

[0102] In yet another embodiment, X is selected from S, SO, SO2 and O, such as S, SO and SO2, with S being preferred.

[0103] In yet another implementation plan, R 1 Selected from H; OH; OC 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OCs substituted with at least one of the following groups. 1-4 Alkyl: phenyl and phenyl groups substituted with one or more groups selected from OH and halogens. In a more preferred embodiment, R 1 Selected from H; OC 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OCs substituted with at least one of the following groups. 1-4 Alkyl: phenyl and phenyl groups substituted with one or more groups selected from OH and halogens. In a further preferred embodiment, R 1 Selected from OC 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OCs substituted with at least one of the following groups. 1-4 Alkyl: phenyl and phenyl groups substituted with one or more groups selected from OH and halogens.

[0104] In another implementation, R 1 Selected from H, OH, OCH3, and OCs optionally substituted with one or more halogens. 1-6 Alkyl groups; such as H, OH, OCH3, and OCH2CF3.

[0105] In yet another implementation plan, B 1The group B1 is selected from heteroaryl groups, optionally substituted with groups selected from: halogen; C2-ynyl; CN; methyl groups optionally substituted with F; and heteroaryl. In yet another embodiment, B1 is selected from heteroaryl groups, optionally substituted with groups selected from: halogen; CN; methyl groups optionally substituted with F; and heteroaryl. Preferably, B1 is selected from pyridyl groups, optionally substituted with groups selected from: Cl; Br; CN; ethynyl; methyl; CF3; pyridine; pyrimidine; oxazole; and thiazole.

[0106] In yet another embodiment, B1 is selected from heteroaryl groups, which are optionally substituted with groups selected from: halogens; C2-alkynyl groups; CN groups; methyl groups optionally substituted with F groups; spiroheterocyclic groups; SC groups optionally substituted with F groups. 1-3 Alkyl; CONR 12 R 13 , where R 12 and R 13 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 Together with the nitrogen, it forms heterocyclic alkyl groups; and heterocycles, such as tetrahydropyridine.

[0107] In yet another embodiment, B1 is selected from pyridinyl, which is optionally substituted with a group selected from the following: Cl; Br; F; ethynyl; N-(2-oxa)-6-azaspiro[3.3]heptyl; CO-azacyclobutyl; CONHCH3; CONHCH2CH3; CON(CH3)2; CN; methyl; SCH3; SCF3; CF3; imidazole; pyridine; pyrimidine; oxazole; and thiazole.

[0108] In yet another embodiment, B1 is selected from pyridinyl, which is substituted with one or more groups selected from Cl, Br, and CN. Typically, B1 is selected from pyridinyl, which is substituted with one, two, or three (such as one or two) groups selected from Cl, Br, and CN.

[0109] In yet another implementation plan, B 1 Selected from heterocyclic alkyl groups, such as tetrahydro-bipyridine.

[0110] In yet another implementation plan, B 1 Selected from heteroaryl groups, which may optionally be substituted with groups selected from: spiroheterocyclic; CONR 12 R 13 , where R 12 and R 13 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl, or R 12 and R 13Together with the nitrogen, a heterocyclic alkyl group is formed. Typically, B1 is selected from pyridinyl, which is optionally substituted with a group selected from the following: N-(2-oxa)-6-azaspiro[3.3]heptyl; CO-azacyclic butyl; CONHCH3; CONHCH2CH3; CON(CH3)2; and imidazole.

[0111] In yet another embodiment, B1 is selected from benzothiazolyl or thiazopyridyl, which is optionally substituted with a group selected from: Cl; Br; F; ethynyl; N-(2-oxa)-6-azaspiro[3.3]heptyl; CO-azacyclobutyl; CONHCH3; CONHCH2CH3; CON(CH3)2; CN; methyl; SCH3; SCF3; CF3; imidazole; pyridine; pyrimidine; oxazole; and thiazole.

[0112] In yet another implementation plan, B 1 Selected from phenyl groups, optionally substituted with groups selected from: halogens; and C groups optionally substituted with F. 1-3 alkyl.

[0113] In yet another implementation plan, B 1 Selected from phenyl groups, optionally substituted with groups selected from: CN; -CONR 6 R 7 , where R 6 and R 7 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl. Typically, B 1 Selected from phenyl groups, which are optionally substituted with groups selected from CN and CONHCH3.

[0114] In yet another embodiment, B1 is selected from phenyl, which is optionally substituted with a group selected from: halogen; CN; -CONR. 6 R 7 , where R 6 and R 7 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl; and C-substituted with F. 1-3 alkyl.

[0115] In yet another embodiment, B1 is selected from phenyl, which is optionally substituted with a group selected from: Cl; F; Br; CN; CONHCH3; and C optionally substituted with F. 1-3 alkyl.

[0116] In yet another embodiment, B1 is selected from phenyl groups, which are substituted with groups selected from Cl, F, and methyl. Typically, B1 is selected from phenyl groups, which are substituted with one, two, or three (such as one or two) groups selected from Cl, F, and methyl.

[0117] In yet another embodiment, the compound of formula (1) is selected from any of the following:

[0118] 3,5-Dichloro-4-fluoro-phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0119] 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

[0120] 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

[0121] 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

[0122] 5-Chloro-2-cyanopyridin-3-yl2-O-benzyl-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0123] 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

[0124] 3,5-Dichloro-4-fluoro-phenyl 3-deoxy-2-O-methyl-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0125] 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside,

[0126] 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside,

[0127] 3,4-Dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0128] 5-Bromo-2-cyanopyridin-3-yl-3-deoxy-3-[4-(4-chloro-thiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0129] 5-Bromo-6-cyano-3-pyridyl-3-deoxy-3-[4-(4-chloro-thiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0130] 5-Chloro-2-cyanopyridin-3-yl-3-deoxy-3-[4-(4-chloro-thiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0131] 5-Chloro-6-cyanopyridin-3-yl-3-deoxy-3-[4-(4-chloro-thiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0132] 5-Chloro-2-cyanopyridin-3-yl-3-deoxy-3-[4-(2-chlorothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0133] 3,5-Dichloro-4-fluoro-phenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0134] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0135] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0136] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside

[0137] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0138] 5-Chloro-2-(pyrimidin-5-yl)-pyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0139] 5-Chloro-2-(pyridin-4-yl)-pyridin-3-yl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0140] 5-Chloro-2-(pyridin-3-yl)-pyridin-3-yl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0141] 5-Chloro-1',2',3',6'-Tetrahydro-[2,4'-bipyridine]-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0142] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside

[0143] 5-Chloro-2-(pyridin-3-yl)-pyridin-3-yl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0144] 5-Chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0145] 3,4-Dichlorophenyl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0146] 5-Chloro-2-(thiazo-2-yl)pyridin-3-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0147] 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,

[0148] 3-Chlorophenyl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0149] 3,5-Dichloro-4-fluoro-phenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0150] 5-Bromo-6-trifluoromethylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside; or

[0151] Its pharmaceutically acceptable salts or solvates.

[0152] In yet another embodiment, the compound of formula (1) is selected from any of the following:

[0153] 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,

[0154] 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

[0155] 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

[0156] 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

[0157] 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

[0158] 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

[0159] 3,5-Dichloro-4-fluorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside,

[0160] 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside,

[0161] 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside,

[0162] 3,4-Dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0163] 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

[0164] 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

[0165] 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

[0166] 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

[0167] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-chlorothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0168] 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,

[0169] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0170] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0171] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside

[0172] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0173] 5-Chloro-2-(pyrimidin-5-yl)-pyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0174] 5-Chloro-2-(pyridin-4-yl)-pyridin-3-yl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0175] 5-Chloro-2-(pyridin-3-yl)-pyridin-3-yl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0176] 5-Chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazolin-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0177] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside

[0178] 5-Chloro-2-(pyridin-2-yl)-pyridin-3-yl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0179] 5-Chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0180] 3,4-Dichlorophenyl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0181] 5-Chloro-2-(thiazo-2-yl)pyridin-3-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0182] 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,

[0183] 3-Chlorophenyl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0184] 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,

[0185] 3-Bromo-2-trifluoromethylpyridin-5-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0186] 5-Bromo-2-cyanopyridin-3-yl-3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0187] 2-Cyano-5-methylpyridin-3-yl-3-deoxy-3-[4-(4-methyltriazol-2-yl)-1H-1,2,3-thiazo-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0188] 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

[0189] 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,

[0190] 5-Chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptyl}-pyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0191] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0192] 5-Cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0193] 3,5-Dichloro-4-fluorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0194] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside,

[0195] 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,

[0196] 3-Cyano-2-(trifluoromethyl)pyridin-5-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0197] 5-Chloro-2-(N-azacyclobutylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0198] 5-Chloro-2-(pyridin-2-yl)-pyridin-3-yl 3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0199] 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

[0200] 5-Chloropyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0201] 5-Bromopyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0202] 5-Chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0203] 3-Chloro-5-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0204] 3-Chloro-4-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0205] 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,

[0206] 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,

[0207] 5-Bromo-2-cyanopyridin-3-yl-3-[4-(4,5-dichlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0208] 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

[0209] 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,

[0210] 5-Bromo-2-cyanophenyl-3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0211] 5-Bromo-2-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0212] 5-Bromo-2-(N-methyl-carbonyl)phenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0213] 5-Bromo-2-(N-methyl-carbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0214] 5-Chloro-2-(N-methyl-carbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0215] 5-Bromo-2-cyanophenyl-3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0216] 5-Bromo-2-cyanopyridin-3-yl-3-[4-(5-chloro-4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0217] 5-Bromo-2-cyanophenyl 3-[4-(5-chloro-4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0218] 2,5-Dichlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0219] 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

[0220] 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

[0221] 5-Bromo-2-fluorophenyl 3-deoxy-3-[4-(4-methylthiazolyl-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0222] 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

[0223] 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

[0224] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0225] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0226] 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0227] 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0228] 5-Chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0229] 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

[0230] 3,4-Dichlorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside,

[0231] 3,4-Dichlorophenyl 3-deoxy-2-O-(2,2,2-trifluoroethyl)-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0232] 5-Ethynylpyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0233] 5-Ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0234] 5-Cyanopyridin-3-yl-3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0235] 5-Cyanopyridin-3-yl-3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0236] 2-Cyano-5-ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0237] 2-Cyano-5-ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0238] 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

[0239] 3,4-Dichlorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside,

[0240] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside,

[0241] 3-Chloro-4-cyanophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0242] 5-Bromo-2-(N,N-dimethylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside,

[0243] 5-Ethynyl-2-(N,N-dimethylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0244] 5-Ethynyl-2-(N-azacyclobutylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0245] 5-Chloro-2-(N-methylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0246] 5-Chloro-2-(N-ethylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0247] 5-Chloro-2-(N-methylcarbamoyl)-3-pyridyl-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,

[0248] 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,

[0249] 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,

[0250] 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,

[0251] 5-Cyano-1,3-benzothiazo-6-yl-3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0252] 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

[0253] 5-Methylthioalkylpyridin-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

[0254] 5-(trifluoromethylthioalkyl)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 solvation thereof.

[0255] In another aspect, the present invention relates to compounds of formula (1) which are used as pharmaceuticals.

[0256] In yet another 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.

[0257] In another aspect, the present invention relates to compounds of formula (1) for use in a method of treating disorders in mammals such as humans related to the binding of galactolectin-1 and / or galactolectin-3 to ligands. In yet another embodiment, the disorder is selected from the group consisting of: inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndrome; fibrosis, such as pulmonary fibrosis, liver fibrosis, renal fibrosis, ophthalmic fibrosis, and fibrosis of the skin and heart; and localized fibrosis, such as Dupuytren's disease and Peyronie's disease. Diseases such as coronary artery stents, bile duct stents, cerebral artery stents, ureteral stents, and other therapies; fibrotic complications; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonia; abnormal scar formation; surgical adhesions; septic shock; cancers such as colorectal cancer, other gastrointestinal cancers such as pancreatic cancer, gastric cancer, biliary tract cancer, lung cancer, mesothelioma, female cancers such as breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube cancer, brain cancers such as medulloblastoma, glioma, meningioma, skeletal and muscular sarcomas and other sarcomas, leukemia and lymphomas such as T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven bone diseases such as osteogenesis imperfecta; pulmonary hypertension; autoimmune diseases such as psoriasis, rheumatoid arthritis, rheumatoid lung disease; Crohn's disease. Diseases such as ulcerative colitis, ankylosing spondylitis, and systemic lupus erythematosus; viral infections such as influenza virus, HIV, herpesvirus, coronavirus, and hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or diseases or conditions related to ocular angiogenesis, such as cancer-related neovascularization; and eye diseases such as age-related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases; diabetes; type 1 diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Loeys-Dietz syndrome; kidney disease; diastolic heart failure; fibrotic lung complications of aPD1 and other CPI therapies; asthma and other interstitial lung diseases, including Hermansky-Pudlak syndrome; liver disorders such as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease; and uterine diseases such as uterine fibroids and uterine or cervical fibrosis.

[0258] In yet another aspect, the present invention relates to a method for treating a disorder in mammals such as humans related to the binding of galactolectin-1 and / or galactolectin-3 to ligands, wherein a therapeutically effective amount of at least one compound of formula (1) of the present invention is applied to the mammal requiring said treatment. In yet another embodiment, said disorder is selected from the group consisting of: inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndrome; fibrosis, such as pulmonary fibrosis, liver fibrosis, renal fibrosis, ophthalmic fibrosis, and fibrosis of the skin and heart; localized fibrosis, such as de Pietrohn's disease and Peroni's disease; fibrotic complications of other therapies such as coronary stents, bile duct stents, cerebral artery stents, ureteral stents; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonia; abnormal scarring; surgical adhesions; septic shock; cancers such as colorectal cancer, other gastrointestinal cancers such as pancreatic cancer, stomach cancer, biliary tract cancer, lung cancer, mesothelioma, female cancers such as breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube cancer, brain cancers such as medulloblastoma, glioma, meningioma, skeletal and muscular sarcomas and other sarcomas, leukemia and lymphomas such as T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven disease. Bone diseases, such as osteogenesis imperfecta; pulmonary hypertension; autoimmune diseases, such as psoriasis, rheumatoid arthritis, rheumatoid lung disease; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections, such as influenza virus, HIV, herpesvirus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or diseases or conditions related to ocular angiogenesis, such as cancer-related neovascularization; and eye diseases, such as age-related angiogenesis. Related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases; diabetes; type 1 diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Lois-Dietz syndrome; nephropathy; diastolic heart failure; fibrotic lung complications of aPD1 and other CPI therapies; asthma and other interstitial lung diseases, including Hermansky-Pudler 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.

[0259] Another aspect of the invention relates to a combination therapy involving the administration of a compound of formula (I) of the invention together with a therapeutically active compound different from that of formula (I) (which may be interchanged with "different therapeutically active compound"). In one embodiment, the invention relates to a combination of a compound of formula (I) and a different therapeutically active compound for treating disorders in mammals related to the binding of galactolectin-1 and / or galactolectin-3 to ligands. Such disorders are disclosed below.

[0260] In one embodiment of the invention, a therapeutically effective amount of at least one compound of formula (I) of the invention, in combination with various therapeutically active compounds, is applied to a mammal in need. In yet another embodiment, a compound of formula (I) in combination with various therapeutically active compounds is applied to a mammal suffering from a disorder selected from the group consisting of: inflammation; fibrosis, such as pulmonary fibrosis, liver fibrosis, kidney fibrosis, ophthalmic fibrosis, and fibrosis of the skin and heart; scarring; keloid formation; abnormal scar formation; surgical adhesions; septic shock; cancers, such as carcinoma, sarcoma, leukemia, and lymphoma, such as T-cell lymphoma; metastatic cancer; autoimmune diseases, such as psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, etc. Spondylitis, systemic lupus erythematosus; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or diseases or conditions related to ocular angiogenesis, such as cancer-related neovascularization; and eye diseases, such as age-related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases, such as diabetes; type 2 diabetes; insulin resistance; obesity; diastolic heart failure; asthma and other interstitial lung diseases, including Hermansky-Pudler syndrome and mesothelioma; liver disorders, such as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease.

[0261] Examples of cancers that can be treated, managed, and / or prevented by applying a compound of formula (I) in combination with various therapeutically active compounds are given from the non-restricted group of cancers selected from: colon cancer, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, chordoma, angiosarcoma, endothelial sarcoma, lymphangiosarcoma, lymphangioendothelial 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, bronchial carcinoma, renal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung cancer, small cell lung cancer, bladder cancer, epithelial carcinoma, glioblastoma, neurogenic cancer. Tumors, craniopharyngioma, schwannoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pineal tumor, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia and lymphoma, acute lymphoblastic leukemia and acute myeloid polycythemia vera, multiple myeloma, Waldenstrom's macroglobulinemia. Macroglobulinemia, heavy chain disease, acute non-lymphocytic 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, gastric cancer, brain cancer, liver cancer, laryngeal cancer, esophageal cancer, breast tumors, childhood acute lymphoblastic leukemia (ALL), thymic ALL, B-cell ALL, acute myeloid leukemia, myelomonocytic leukemia, acute megakaryoblastic leukemia, Burkitt's lymphoma, acute myeloid leukemia, chronic myeloid leukemia, and T-cell leukemia, large and small 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.

[0262] In some aspects of the invention, the administration of at least one compound of formula (I) and at least one additional therapeutic agent exhibits a synergistic therapeutic effect. In some aspects of the method of the invention, the same measurement of the response to treatment observed after administration of both at least one compound of formula (I) and the additional therapeutic agent is improved relative to the measurement of the response to treatment observed after administration of either at least one compound of formula (I) alone or the additional therapeutic agent alone.

[0263] Another aspect of the invention relates to a combination therapy involving the administration of a compound of formula (I) of the invention together with an antifibrotic compound different from that of formula (I) to a mammal in need. In yet another embodiment, such an antifibrotic compound may be selected from the group of non-limiting antifibrotic compounds: pirfenidone, nintedanib, simtuzumab (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.

[0264] Another aspect of the invention relates to a combination therapy involving the administration of a compound of formula (I) in combination with other conventional cancer treatments, such as chemotherapy or radiotherapy, or treatment with immunostimulants, gene therapy, antibody treatment and treatment using dendritic cells, or mRNA-based therapy (including mRNA-based cancer vaccines), and / or virus-based cancer vaccines, to a mammal in need.

[0265] In one embodiment, the compound of formula (I) is administered together with at least one other therapeutic agent selected from antitumor chemotherapeutic agents. In yet another embodiment, the antitumor chemotherapeutic agent is selected from: all-trans retinoic acid, Actimide, azacitidine, imidazoline, bleomycin, carboplatin, capecitabine, cisplatin, clomibucil, cyclophosphamide, cytarabine, docetaxel, deoxyfluorouridine, doxorubicin, epirubicin, etoposide, fludarabine, fluorouracil, gemcitabine, hydroxyurea, idarubicin, irinotecan, lenalidomide, leucovorin, nitrogen mustard, melphalan, mercaptopurine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, Revlimid, temozolomide, teniposide, thioguanine, pentorubicin, vinblastine, vincristine, vinorelbine, and vinorelbine. In one embodiment, the chemotherapeutic agents used in the combination of the pharmaceutical agents of the present invention can themselves be a combination of different chemotherapeutic agents. Suitable combinations include FOLFOX and IFL. FOLFOX is a combination comprising 5-fluorouracil (5-FU), leucovorin, and oxaliplatin. IFL treatment comprises irinotecan, 5-FU, and leucovorin.

[0266] In yet another embodiment of the invention, the additional conventional cancer treatment includes radiation therapy. In some embodiments, radiation therapy includes localized radiation delivered to the tumor. In some embodiments, radiation therapy includes whole-body irradiation.

[0267] In other embodiments of the invention, the additional cancer treatment is selected from the group consisting of immunostimulants, such as cytokines and antibodies. Such cytokines may be selected from, but are not limited to, the group consisting of GM-CSF, type I IFN, interleukin-21, interleukin-2, interleukin-12, and interleukin-15. Antibodies are preferably immunostimulatory antibodies, such as anti-CD40 or anti-CTLA-4 antibodies. Immunostimulants may also be substances capable of consuming immunosuppressive cells (e.g., regulatory T cells) or factors, such as E3 ubiquitin ligases. E3 ubiquitin ligases (HECT, RING, and U-box proteins) have emerged as key molecular regulators of immune cell function, and each can participate in the regulation of the immune response during infection by targeting specific inhibitory molecules for proteolytic destruction. Several HECT and RING E3 proteins are now also associated with the induction and maintenance of immune self-tolerance: c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4 each negatively regulate the production and proliferation of T cell growth factors.

[0268] In some embodiments of the invention, the compound of formula (I) is administered together with at least one additional therapeutic agent selected from checkpoint inhibitors. In some embodiments of the invention, the checkpoint inhibitor acts on one or more of the following non-limiting target groups: CEACAM1, galactolectin-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 together with the compound of formula (I) are anti-PD-1 inhibitors: nivolumab, pembrolizumab, and cimiplimab. Anti-PD-L1 inhibitors include atezolizumab, avelumab, and durvalumab, while an anti-CTLA-4 inhibitor is ipilimumab. Each of these checkpoint inhibitors can be combined with any compound of formula (1) to form the subject of an embodiment.

[0269] In some embodiments of the invention, the compound of formula (I) is administered together with at least one additional therapeutic agent selected from indoleamine-2,3-dioxygenase (IDO) inhibitors.

[0270] In some embodiments of the invention, the compound of formula (I) is administered together with at least one additional therapeutic agent selected from one or more CTLA4 pathway inhibitors. In some embodiments, the CTLA4 pathway inhibitor is selected from one or more antibodies targeting CTLA4.

[0271] In some embodiments of the invention, the compound of formula (I) is administered together with at least one additional therapeutic agent selected from one or more PD-1 / PD-L pathway inhibitors. In some embodiments, the one or more PD-1 / PD-L pathway inhibitors are selected from one or more antibodies or antibody fragments targeting PD-1, PD-L1, and / or PD-L2, or other methods that can induce anti-PD1 antibodies, such as the introduction of mRNA-based genetic material that provides for the in vivo production of anti-PD1 or anti-PDL1 antibodies or fragments of such antibodies.

[0272] In yet another aspect, the present invention relates to 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 As defined in Equation 1 above;

[0273]

[0274] a1) make the compound of formula I (where X) 1 and X 2 The compounds (forming protecting groups, such as benzylidene) are reacted in an inert organic solvent, such as DCM, in the presence of an acid, such as TFA, and then optionally neutralized with a base, such as triethylamine, at a temperature below room temperature to give the compound of formula II; optionally, the compound of formula I (where X) is reacted with a base, such as triethylamine, to form a protecting group, such as benzylidene, in the presence of an acid, such as TFA, in an inert organic solvent 1 and X 2 It consists of two protecting groups, such as acetate, reacted 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, and then neutralized with an acid such as HCl to give the compound of formula II.

[0275] In yet another aspect, the present invention relates to 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 As defined in Equation 1 above;

[0276]

[0277] a2) make the compound of formula III (where X) 3 and X 4(is hydrogen or a protecting group, such as an acetate) and formula B 1 The -SH compound is reacted in an organic solvent such as toluene, optionally in the presence of a catalyst such as oxotrichloro[(dimethyl sulfide)triphenylphosphine oxide]rhenium(V) or BF3OEt2, optionally at elevated temperatures, to give the compound of formula IV; when X 3 and X 4 When the protecting group (such as acetate) is present, it can be removed in a separate step in the presence of a base (such as triethylamine, LiOH, or sodium methoxide) in a suitable solvent (such as methanol and water) to obtain the compound of formula IV.

[0278] In yet another aspect, the present invention relates to 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 As defined in Equation 1 above;

[0279]

[0280] a3) Make the compound of formula V and formula A 1 -CC-H or A 1 The compounds of -CC-TMS are reacted in an inert solvent (such as DMF or acetonitrile) with a base such as diisopropylethylamine or sodium L-ascorbate, catalyzed by a copper salt (such as CuI or copper sulfate (II)) and optionally with a reagent such as CsF to provide compounds of formula II.

[0281] In yet another aspect, the present invention relates to a method for preparing a compound of formula VIII or a pharmaceutically acceptable salt or solvate thereof, comprising steps a4-a5, wherein A 1 and B 1 As defined in Equation 1 above;

[0282]

[0283] a4) Make the compound of formula VI and formula X 3 -L 1 Compounds (where X) 3 Together with O is OX 3 It is selected from c) under the definition of R1 in Equation 1 above and L 1 The leaving group, such as a halogen (such as Cl, Br, I) or a sulfate ester (such as methanesulfonate, toluenesulfonate or trifluoromethanesulfonate), is reacted in an organic solvent such as DMF, optionally in the presence of a reagent such as NaH, CsCO3 or AgO, to give a compound of formula VII.

[0284] a5) Make the compound of formula VII and formula A 1 -CC-H or A 1 The compounds of -CC-TMS are reacted in an inert solvent (such as DMF or acetonitrile) with a base such as diisopropylethylamine or sodium L-ascorbate, catalyzed by a copper salt (such as CuI or copper(II) sulfate), and optionally with a reagent such as CsF, to provide compounds of formula VIII.

[0285] In yet another aspect, the present invention relates to a method for preparing a compound of formula VIII or a pharmaceutically acceptable salt or solvate thereof, comprising steps a6-a7, wherein A 1 B 1 and R 1 As defined in Equation 1 above;

[0286]

[0287] a6) Make the compound of formula IX and formula A 1 -CC-H or A 1 The compounds of -CC-TMS are reacted in an inert solvent (such as DMF or acetonitrile) with a base such as diisopropylethylamine or sodium L-ascorbate, catalyzed by a copper salt (such as CuI or copper(II) sulfate), and optionally with a reagent such as CsF, to provide compounds of formula X.

[0288] a7) Make the compound of formula X with formula X 3 -L 1 Compounds (where X) 3 Together with O is OX 3 It is selected from c) under the definition of R1 in Equation 1 above and L 1 A compound of formula VIII is provided by reacting a leaving group, such as a halogen (such as Cl, Br, I) or a sulfate ester (such as methanesulfonate, toluenesulfonate or trifluoromethanesulfonate) in an organic solvent such as DMF, optionally in the presence of a reagent such as NaH, CsCO3 or AgO.

[0289] In yet another aspect, the present invention relates to 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 As defined in Equation 1 above;

[0290]

[0291] a8) makes the compound of formula XI (where B) 2 B selected from Equation 1 1 Parts b) and d) and L3 A halogenated group (such as I, Br, or Cl) reacts with an organometallic compound (such as Zn(CN)2) in the presence of Zn and 1,1'-bis(diphenylphosphino)ferrocene and Pd2(dba)3 in a suitable organic solvent such as DMF, optionally at elevated temperatures, to give compound XII, wherein X... 6 Defined as -CN; optionally, a compound of formula XI as defined above is reacted with borocyclohexane such as 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborane 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 at elevated temperatures to give a compound of formula XII, wherein X 6 Defined as methyl; optionally, a compound of formula XI as defined above is reacted with a tin alkane such as tributyl(oxazol-2-yl)stanane or tributyl(thiazol-2-yl)stanane in the presence of an organometallic catalyst such as Pd(PPh3)4, optionally in the presence of CsF, at an elevated temperature to give a compound of formula XII, wherein X 6 It is optionally a substituted five- or six-membered heteroaromatic ring; optionally, the compound of formula XI as defined above is reacted with a heterocyclic boronic ester such as 4-(4,4,5,5-tetramethyl-1,3,2-dioxacyclopentaborane-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester in the presence of a catalyst such as bis(triphenylphosphine)palladium(II) chloride, optionally in the presence of a base such as potassium carbonate, optionally in the presence of water, in an organic solvent such as 1,4-dioxane, optionally at an elevated temperature to give the compound of formula XII, wherein X 6 Defined as a five- or six-membered heteroaromatic ring or heterocycle; optionally, the compound of formula XI can be reacted with an alkyne or a protected alkyne (such as ethynyl(trimethyl)silane) in an inert solvent such as THF in the presence of one or more organometallic reagents (such as CuI, bis(triphenylphosphine)palladium(II) chloride). Optionally in the presence of an organic base (such as triethylamine or DIPEA). Optionally at elevated temperatures, such as 30°C–80°C. If the alkyne reagent is protected with a silyl protecting group (such as trimethylsilane), the protecting group can be removed in successive steps by adding a reagent such as TBAF or KF.

[0292] In yet another aspect, the present invention relates to a method for preparing a compound of formula III or a pharmaceutically acceptable salt or solvate thereof, comprising steps a9-a10, wherein A 1 As defined in Equation 1 above, and X 7 and X 8 Optionally and independently selected from hydrogen and acetate;

[0293]

[0294] a9) Make the compound of formula XIII and formula A 1 -CC-H or A 1 The compounds of -CC-TMS are reacted in an inert solvent (such as DMF or acetonitrile) with a base such as diisopropylethylamine or sodium L-ascorbate, catalyzed by a copper salt (such as CuI or copper(II) sulfate), and optionally with a reagent such as CsF, to provide compounds of formula XIV.

[0295] a10) React the compound of formula XIV with an acid (such as HBr and acetic acid) in an inert solvent such as DCM for 0-10 h, after which the product is separated and further reacted in a solvent such as acetonitrile in the presence of ammonium chloride and zinc for 3-7 days to give the compound of formula III.

[0296] In yet another aspect, the present invention relates to a method for preparing a compound of formula XIX or a pharmaceutically acceptable salt or solvate thereof, comprising steps a11-a14, wherein A 1 and B 1 As defined in Equation 1 above;

[0297]

[0298] a11) React compound XV with a chlorinating agent (such as dichloromethyl methyl ether or PCl5) in an inert solvent (such as dichloromethane or chloroform) in the presence of a Lewis acid (such as BF3Et2O) to give a compound of formula XVI, wherein L 2 It is defined as chlorine.

[0299] a12) React the compound of formula VII with a nucleophile as shown in formula HS-B 1 The compound is reacted in an inert solvent such as DMF in the presence of a base (such as sodium hydride) to give the compound of formula IX.

[0300] a13) React the 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, and then neutralize with an acid such as HCl to give the compound of formula XVIII.

[0301] a14) React the compound of formula XVIII with a reagent such as benzaldehyde dimethyl acetal in an inert solvent (such as DMF or toluene) in the presence of an acid such as D(+)-10-camphorsulfonic acid, optionally distilling off methanol at an elevated temperature and optionally under reduced pressure to give the compound of formula XIX.

[0302] In yet another aspect, the present invention relates to a method for preparing a compound of formula VI or a pharmaceutically acceptable salt or solvate thereof, comprising steps a15-a20, wherein A 1 and B 1 As defined in Equation 1 above, X 9 and X 10 Optionally and independently selected from hydrogen and acetate or together forming a protecting group such as benzylidene;

[0303]

[0304] a15) React a compound of formula XX with a reagent such as benzaldehyde dimethyl acetal in an inert solvent (such as DMF or toluene) in the presence of an acid such as D(+)-10-camphorsulfonic acid, optionally distilling off methanol at an elevated temperature and optionally under reduced pressure to give a compound of formula XXI, wherein X 9 and X 10 Together they form benzylidene.

[0305] a16) React the compound of formula XXI with a methylating agent such as methyl iodine in the presence of a base such as sodium hydride in an inert solvent such as DMF to give the compound of formula XXII.

[0306] a17) React 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 It is defined as an acetate.

[0307] a18) React compound XXIII with a chlorinating agent (such as dichloromethyl methyl ether or PCl5) in an inert solvent (such as dichloromethane or chloroform) in the presence of a Lewis acid (such as BF3Et2O) to give a compound of formula XXIV.

[0308] (a19) React the compound of formula XXIV with a thioacetate such as potassium thioacetate in an inert solvent such as DMF to give the compound of formula XXV.

[0309] a20) makes compounds of formula XXV react with substances such as B 1 -L 4 (where L) 4 Compounds defined as leaving groups (such as fluoro groups or sulfate esters, such as trifluoromethanesulfonates) are reacted in an inert solvent such as DMF in the presence of a base such as diethylamine to give compounds of formula XXVI.

[0310] In yet another aspect, the present invention relates to a preparative formula A 1 -CC-H or A 1A method for compounding -CC-TMS, comprising step a20, wherein A 1 As defined in equation (1) above:

[0311] a21) Using palladium catalysts such as bis(triphenylphosphine)palladium-(II) chloride, copper iodide, and bases such as diisopropylethylamine, formula A is... 1 -L 5 Compounds (where L) 5 Defined as a leaving group, such as chlorine or bromine, reacts with trimethylsilane-acetylene in an inert solvent such as tetrahydrofuran (THF) to give formula A. 1 -CC-H or A 1 Compounds of -CC-TMS.

[0312] In yet another aspect, the present invention relates to a method for preparing a compound of formula XXVII, comprising steps a22-a23:

[0313]

[0314] 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.

[0315] a23) React the compound of formula XXVII with thiourea in an inert solvent such as DMF to give the compound of formula XXVIII.

[0316] In yet another aspect, the present invention relates to a method for preparing a compound of formula XXXI, comprising steps a24-a25, wherein B 1 As defined in equation (1) above;

[0317]

[0318] Compounds of formula XXIX (a24) can form corresponding diazo compounds after treatment with sodium nitrite. These compounds can further react with sulfur sources such as potassium ethyl xanthate to form compounds of formula XXX.

[0319] a25) Reacting a compound of formula XXX with a base such as potassium hydroxide yields a compound of formula XXXI.

[0320] In yet another aspect, the present invention relates to a method for preparing a compound of formula XXXIII, comprising step a26, wherein B 1 As defined in equation (1) above;

[0321]

[0322] a25) React the compound of formula XXXII with Na2S·10H2O in the presence of a base such as NaOH in an inert solvent such as DMF to give the compound of formula XXXIII.

[0323] In yet another aspect, the present invention relates to a method for preparing a compound of formula XXXVII, comprising steps a27-a29, wherein B 1 As defined in equation (1) above;

[0324]

[0325] a27) Using a base such as sodium hydride, the compound of formula XXXIV is reacted with an activated thioamide such as dimethylcarbamoyl chloride in an inert solvent such as DMF to give the compound of formula XXXV.

[0326] a28) The compound of formula XXXV is heated at an elevated temperature to form compound XXXVI.

[0327] (a29) Reacting a compound of formula XXXVI with a base such as potassium hydroxide yields a compound of formula XXXVII.

[0328] In yet another aspect, the present invention relates to a method for preparing a compound of formula XXXIX, comprising step a30, wherein B 1 As defined in equation (1) above;

[0329]

[0330] (a30) React a compound of formula XXXVIII (where L is a leaving group, such as bromine) with CuCN in an inert solvent such as dimethylformamide, optionally at an elevated temperature, to give a compound of formula XXXIX.

[0331] In yet another aspect, the present invention relates to a method for preparing a compound of the formula XLI, comprising step a31, wherein B 1 As defined in equation (1) above;

[0332]

[0333] a31) makes compounds of formula XL (where B) 1 As defined above, and L is a leaving group (such as iodine), KF and CuI are optionally reacted at elevated temperatures 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-pyrrolidone (NMP) and 3,5-dichloro-2-iodopyridine is added to give a compound of formula XLI.

[0334] In yet another aspect, the present invention relates to a method for preparing B 1 and R 1 A method for a compound of formula V as defined in formula 1 or a pharmaceutically acceptable salt or solvate thereof, comprising steps a31 and a32;

[0335]

[0336] (a32) React the compound of formula XLII with a sulfur nucleophile such as potassium thioacetate to give compound XLVI in an inert solvent such as DMF.

[0337] a33) Using a base such as dimethylamine to react the compound of formula XLVI with formula B 1 A compound of formula V is reacted in an inert solvent such as DMF (where L is defined as a leaving group, such as fluorine, chlorine or bromine) to give a compound of formula V.

[0338] —In yet another aspect, the present invention relates to a method for preparing a compound of formula XLIV, comprising step a34, wherein A 1 and B 1 As defined for Equation 1;

[0339]

[0340] a34) make X 11-13 Compounds of formula XLIII with protecting groups (such as acetates) are reacted 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, and then neutralized with an acid such as HCl to give compounds of formula XLIV.

[0341] In yet another aspect, the present invention relates to a method for preparing A 1 and B 1 A method for a compound of formula XLV as defined in formula 1 or a pharmaceutically acceptable salt or solvate thereof, comprising step a35;

[0342]

[0343] a35) Reacting a compound of formula XLIV with a reagent such as benzaldehyde dimethyl acetal in an inert solvent (such as DMF or toluene) in the presence of an acid such as D(+)-10-camphorsulfonic acid or p-toluenesulfonic acid, optionally distilling off methanol at elevated temperature and optionally under reduced pressure to give a compound of formula XLV, wherein X 14 and X 15 Together they form benzylidene.

[0344] In yet another aspect, the present invention relates to a method for preparing a compound of formula XLVII, wherein A 1 As defined for compounds of formula 1, and B 3 B selected from the compounds of Formula 1 1 Parts b) and d), where X 17 Defined as -CONR 6 R 7 or -CONR 12 R 13 (where R) 6 R 7 R 12 and R 13 As defined for compounds of Formula 1), methyl, heterocyclic, -CN, ethynyl, spiroheterocyclic, CONH2, COOH, -SCH3, -COOCH3, the method includes step a36;

[0345]

[0346] a36) makes compounds of formula XLVI (where X 16 Defined as -COOH) with amine reagents such as HNR 6 R 7 or HNR 12 R 13 The compound is reacted, optionally in the presence of an amide coupling agent such as HATU, in the presence of an organic base such as DIPEA, in an inert solvent such as DMF, to give the compound of formula XLVII, wherein X 17 Defined as -CONR 6 R 7 or CONR 12 R 13 Optionally, make compounds of formula XLVI (where X...) 16 (I, Br, and Cl) is a halogen group and reacts with heterocyclic borosilicates such as 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborane in the presence of Pd(PPh4)3 and K2CO3 in an inert solvent such as dioxane, optionally at elevated temperatures and optionally under an inert atmosphere, to give the compound of formula XLVII, wherein X is a halogen group. 17 Defined as methyl; optionally, compounds of formula XLVI (where X is a base such as bis(triphenylphosphine)palladium(II) chloride) are made using organometallic reagents such as bis(triphenylphosphine)palladium(II) chloride and bases such as K₂CO₃. 16Halogenated groups, such as I, Br, and Cl), react with heterocyclic dioxanes (such as 5-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)pyrimidine, 4-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)pyridine, 4-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester) in an inert solvent such as 1,4-dioxane / water to give the compound of formula XLVII, wherein X 17 Defined as a heterocyclic compound, it is optionally heated to 100°C within 1 hour in a microwave reactor; optionally, a compound of formula XLVI (where X is a heterocyclic compound) is formed using an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and a base such as K₂CO₃. 16 (I) Halogen groups, such as I, Br, and Cl, react with heterocyclic borates such as 3-pyridylboronic acid in an inert solvent such as DMF at room temperature to give the compound of formula XLVII, wherein X 17 Defined as heterocyclic; optionally, a compound of formula XLVI is formed by reacting CsF with an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride or palladium tetrakis (where X... 16 A halogenated group (such as I, Br, and Cl) reacts with heterocyclic tinanes (such as tributyl-(2-pyridyl)tinane, tributyl(oxazol-2-yl)tinane, tributyl(thiazol-2-yl)tinane) in an inert solvent such as DMF at room temperature or elevated temperature to give the compound of formula XLVII, wherein X is a halogenated group (such as I, Br, and Cl) reacting ..., tributyl(thiazol-2-yl)tinane, tributyl(thiazol-2-yl)tinane, tributyl(thiazol-2-yl)tinane 17 Defined as heterocyclic; optionally, compounds of formula XLVI (where X is a benzylacetone) are made using organometallic reagents such as Pd2 (dibenzylacetone) and Zn. 16 (A halogen group, such as I, Br, and Cl) reacts with an organometallic reagent such as Zn(CN)₂ in an inert solvent such as DMF at elevated temperatures to give the compound of formula XLVII, wherein X is a halogen group. 17 Defined as -CN; optionally, make compounds of formula XLVI (where X 16 The reaction is a halogen group (such as I, Br, and Cl) with an acetylenic group or a TMS-acetylenic group in the presence of an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and CuI, in the presence of an organic base, in an inert solvent such as DMF, optionally at elevated temperatures, to give the compound of formula XLVII, wherein X 17 Defined as acetylene; optionally, an organic base such as DIPEA is used in the microwave reactor to make a compound of formula XLVI (where X... 16(I, Br and Cl) reacts with heterocyclic or spirocyclic compounds (such as spirocyclic compounds, such as N-(2-oxa)-6-azaspiro[3.3]heptyl) in an inert solvent such as DMF at elevated temperatures such as 130 °C to give the compound of formula XLVII, wherein X is a halogen group, such as I, Br and Cl) reacting ... to give the compound of formula XLVII, wherein X is a halogen group, such as I, Br and Cl) reacting with heterocyclic or spirocyclic compounds (such as spirocyclic compounds, such as N-(2-oxa)-6-azaspiro[3.3]heptyl) in an inert solvent such as DMF at elevated temperatures such as 130 °C to give the compound of formula XLVII, wherein X is a halogen group, such as I, Br and Cl) reacting with heterocyclic or spirocyclic compounds (such as spirocyclic compounds, such as N-(2-oxa)-6-azaspiro[3.3]heptyl) in an inert 17 Defined as a heterocyclic or spirocyclic compound; optionally, compounds of formula XLVI (where X) can be used. 16 (Is a cyano group) reacts with a base such as sodium hydroxide at elevated temperatures in a solvent such as ethanol and water to give a compound of formula XLVII, wherein X is a cyano group. 17 It is -COOH; optionally, make the compound of formula XLVI (where X is -COOH) 16 Yes - COOX 22 And X 22 A compound of formula XLVII is given by reacting a base such as lithium hydroxide or sodium hydroxide with water, optionally mixed with another organic solvent such as ethanol or acetonitrile, at elevated temperature, wherein X is defined as an aryl or optionally aryl-substituted straight-chain or branched C1-C5 alkyl group. 17 It is -COOH; optionally, make the compound of formula XLVI (where X is -COOH) 16 (I, Br, and Cl) are halogen groups that react with alkyl thiols, such as sodium methanethiolate, in a solvent such as DMF to give compounds of formula XLVII, wherein X 17 It is -SCH3; optionally, make compounds of formula XLVI (where X 16 (COOH) reacts with alkyl halides such as methyl iodine in a solvent such as DMF in the presence of a base such as CsCO3 to give a compound of formula XLVII, wherein X 17 It is -COOCH3.

[0347] In yet another aspect, the present invention relates to a method for preparing a compound of the formula XLIX, wherein B 4 B selected from Equation 1 1 Parts b) and d), where X 17 Defined as -CONR 6 R 7 or -CONR 12 R 13 (where R) 6 R 7 R 12 and R 13 As defined with respect to Formula I), methyl, heterocyclic, -CN, ethynyl, spiroheterocyclic, CONH2,COOH, -SCH3, -COOCH3), the method includes step a37;

[0348]

[0349] a37) makes a compound of formula XLVIII (where X 18 Defined as -COOH) with amine reagents such as HNR 6 R 7 or HNR 12 R 13 The compound is reacted, optionally in the presence of an organic base such as DIPEA, in an inert solvent such as DMF in the presence of an amide coupling agent such as HATU, to give the compound of formula XLIX, wherein X 19 Defined as -CONR 6 R 7 or CONR 12 R 13 Optionally, make compounds of formula XLVIII (where X...) 18 (I, Br, and Cl) is a halogen group and reacts with heterocyclic borosilicates such as 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborane in the presence of Pd(PPh4)3 and K2CO3 in an inert solvent such as dioxane, optionally at elevated temperatures and optionally under an inert atmosphere, to give the compound of formula XLIX, wherein X is a halogen group. 19 Defined as methyl; optionally, using organometallic reagents such as bis(triphenylphosphine)palladium(II) chloride and bases such as K₂CO₃ to form compounds of formula XLVIII (where X... 18 Halogenated groups, such as I, Br, and Cl), react with heterocyclic dioxanes (such as 5-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)pyrimidine, 4-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)pyridine, 4-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester) in an inert solvent such as 1,4-dioxane / water to give the compound of formula XLIX, wherein X 19 Defined as a heterocyclic compound, optionally heated to 100°C within 1 hour in a microwave reactor; optionally, a compound of formula XLVIII (where X is a heterocyclic compound) is formed using an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and a base such as K₂CO₃. 18 (I) Halogen groups, such as I, Br, and Cl, react with heterocyclic borates such as 3-pyridylboronic acid in an inert solvent such as DMF at room temperature to give the compound of formula XLIX, wherein X is a halogen group. 19 Defined as heterocyclic; optionally, using an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride or palladium tetrachloride, optionally with CsF, to form a compound of formula XLVIII (where X... 18A halogenated group (such as I, Br, and Cl) reacts with heterocyclic tinanes (such as tributyl-(2-pyridyl)tinane, tributyl(oxazol-2-yl)tinane, tributyl(thiazol-2-yl)tinane) in an inert solvent such as DMF at room temperature or elevated temperature to give the compound of formula XLIX, wherein X is a halogenated group (such as I, Br, and Cl) reacting ... 19 Defined as heterocyclic; optionally, compounds of formula XLVIII (where X is a benzylacetone) are made using organometallic reagents such as Pd2 (dibenzylacetone) and Zn. 18 (Halogen groups, such as I, Br, and Cl) react with organometallic reagents such as Zn(CN)₂ in an inert solvent such as DMF at elevated temperatures to give the compound of formula XLIX, where X is a halogen group. 19 Defined as -CN; optionally, make compounds of formula XLVIII (where X...) 18 The reaction is a halogen group (such as I, Br, and Cl) with an acetylenic group or a TMS-acetylenic group in the presence of an organometallic reagent such as bis(triphenylphosphine)palladium(II) chloride and CuI, in the presence of an organic base, in an inert solvent such as DMF, optionally at elevated temperatures, to give the compound of formula XLIX, wherein X is a halogen group (such as I, Br, and Cl) reacting ... 19 Defined as ethynyl; optionally, in a microwave reactor, an organic base such as DIPEA is used to react a compound of formula XLVIII (where X18 is a halogen, such as I, Br, and Cl) with a heterocyclic or spirocyclic (such as a spirocyclic, such as N-(2-oxa)-6-azaspiro[3.3]heptyl) in an inert solvent such as DMF at an elevated temperature such as 130 °C to give a compound of formula XLIX, wherein X19 is defined as a heterocyclic or spirocyclic; optionally, a compound of formula XLVIII (where X18 is a halogen, such as I, Br, and Cl) can be reacted .... 18 (Is a cyano group) reacts with a base such as sodium hydroxide at elevated temperatures in a solvent such as ethanol and water to give a compound of formula XLIX, wherein X is a cyano group. 19 It is -COOH; optionally, a compound of formula XLVIII (where X is -COOH) is used. 18 Yes - COOX 22 And X 22 A compound of formula XLIX is obtained by reacting a base such as lithium hydroxide or sodium hydroxide with water, optionally mixed with another organic solvent such as ethanol or acetonitrile, at elevated temperature, wherein X is defined as an aryl or optionally aryl-substituted straight-chain or branched C1-C5 alkyl group. 19 It is -COOH; optionally, a compound of formula XLVIII (where X is -COOH) is used. 18 (I) Halogen groups, such as I, Br, and Cl, react with alkyl thiols, such as sodium methanethiolate, in a solvent such as DMF to give compounds of formula XLIX, wherein X 19 It is -SCH3; optionally, make a compound of formula XLVIII (where X... 18(COOH) reacts with alkyl halides such as methyl iodine in a solvent such as DMF in the presence of a base such as CsCO3 to give a compound of formula XLIX, wherein X 19 It is -COOCH3.

[0350] In yet another aspect, the present invention relates to a compound of the preparative formula XLXII (in which B 1 As defined in Equation 1, and X 20 The method (defined as a protecting group), steps a38-a39;

[0351]

[0352] a38) Make the compound of formula L and formula X 20 -SH compounds (where X 20 The protecting group (such as benzyl) is reacted in the presence of a base such as DIPEA in an inert solvent such as dioxane at an elevated temperature to give a compound of formula LI; optionally, the compound of formula L is reacted with (2,4-dimethoxyphenyl)methanethiol in the presence of an organometallic ligand such as bis(dibenzylideneacetone)palladium, or optionally in the presence of a ligand such as 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene, to give a compound of formula LI.

[0353] 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.

[0354] In yet another aspect, the present invention relates to a compound of the preparative formula LIV (in which B) 5 X 22 B is defined as in equations b) and d) of equation 1. 1 The method;

[0355]

[0356] a40) makes compounds of formula LIII (where X) 21 (defined as cyano) reacts with 2,2-dimethoxyethylamine 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, wherein X 22 It's imidazole. Optionally, make compounds of formula LIII (where X) 21 A compound defined as SH) reacts with a compound defined as 3,3-dimethyl-1-(trifluoromethyl)-1,2-benzoiodopyrazine in a solvent such as DCM to give a compound of formula LIV, wherein X 22 It's CF3.

[0357] In yet another aspect, the present invention relates to a method for preparing formula B by means of... 1 -CH3 compounds (where B) 1 As defined in parts b) and d) of Formula 1: to make compound B 1 -Br reacts with 2,4,6-trimethyl-1,3,5,2,4,6-trioxaborane in the presence of Pd(PPh4)3 and K2CO3 in an inert solvent such as dioxane, optionally at elevated temperatures and optionally under an inert atmosphere.

[0358] In reaction steps a1 to a40 above, whenever diastereomers are prepared, they can be separated by chromatography, such as using HPLC. Furthermore, in steps a1 to a40 above, anodic sulfur can be replaced by O, SO, or SO2 under similar reaction conditions to prepare analogs in which S has been substituted. Detailed Implementation

[0359] The compounds of formula (1) of this invention differ from those of prior art compounds, particularly in that the pyranose ring is α-D-galactopyranose. It is important to emphasize that the α and β anomers are very different isomers, and it would not be obvious to a person skilled in the art that the expected identical or similar activities of the two anomers are readily apparent. Therefore, the α and β anomers generally do not possess the same activity, and this is common knowledge to a person skilled in the art. The compounds of this invention are novel α-D-galactopyranose compounds that unexpectedly exhibit very high affinity and specificity for galactolectin-1 and are considered novel drug candidates with potent efficacy. Some of these novel α-D-galactopyranose compounds possess both affinity for galactolectin-1 and galactolectin-3 and therefore have a broader spectrum of disease treatment compared to selective galactolectin-1 inhibitors.

[0360] In a broad sense, the present invention relates to a D-galactopyranose compound of formula (1).

[0361]

[0362] in

[0363] The pyranose ring is α-D-galactopyranose, and A1, R1, X, and B1 are as defined above.

[0364] When A1 is Equation 2, its preferred choice is...

[0365]

[0366] When A1 is

[0367] And when X is S, then R1 is selected from OC. 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OCs substituted with at least one of the following groups. 1-4 Alkyl: phenyl and phenyl substituted with one or more groups selected from OH and halogens, and B1 is selected from pyridyl, optionally substituted with groups selected from: Cl, Br or CN; C2-alkynyl; methyl; CF3; pyridine; pyrimidine; oxazole; and thiazole; and phenyl, optionally substituted with groups selected from: halogen, CN, -CONR 6 R 7 (where R) 6 and R 7 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl), and C optionally substituted with F 1-3 Alkyl group. Preferably, R 1 The group is selected from methoxy, methoxy substituted with a phenyl group, and methoxy substituted with a phenyl group substituted with one to three groups selected from OH and halogens (such as F and Cl). Preferably, B1 is selected from pyridyl, substituted with a group selected from Cl, Br, C2-alkynyl, CN; and phenyl substituted with a group selected from one to three halogens, such as F, Br and / or Cl; CN and CONR. 6 R 7 , where R 6 and R 7 Independently selected from H and C 1-3 alkyl.

[0368] When A1 is

[0369] And when X is S, then R1 is selected from H; OH; OC. 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OCs substituted with at least one of the following groups. 1-4 Alkyl group: phenyl and phenyl group substituted with one or more groups selected from OH and halogens, and B1 is selected from pyridyl group, which is optionally substituted with substituents selected from: Cl, Br, CN, C2-alkynyl, methyl, CF3, -CONR 12 R 13 , where R 12 and R 13 Independently selected from H and C 1-3 Alkyl, cyclopropyl, and isopropyl, or R 12 and R 13 Together with the nitrogen, it forms a heterocyclic alkyl group; pyridine, pyrimidine, oxazole, and thiazole, or a phenyl group optionally substituted with a group selected from: Br, Cl, CN, and CONR. 6 R 7 , where R6 and R 7 Independently selected from H and C 1-3 Alkyl group. Preferably, R1 is selected from H, OH, methoxy, or ethoxy, such as methoxy. Preferably, B1 is selected from pyridyl group substituted with one to three substituents, said substituent being selected from Cl, C2-alkynyl, methyl, Br, CO-azacyclobutyl, CON(CH3)2, CONHCH3, CONHCH2CH3, pyridyl, or CN. Preferably, B1 is selected from phenyl group substituted with one to three substituents, said substituent being selected from Br, Cl, CN, and CONHCH3.

[0370] When A1 is

[0371] And when X is S, then R1 is selected from OC. 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OCs substituted with at least one of the following groups. 1-4 Alkyl: phenyl and phenyl substituted with one or more groups selected from OH and halogens, and B1 is selected from pyridyl, which is optionally substituted with groups selected from: Cl, Br, C2-alkynyl, CN; methyl; CF3; pyridine; pyrimidine; oxazole; and thiazole; and phenyl, which is optionally substituted with groups selected from: halogens and C2-substituted with F. 1-3 Alkyl group. Preferably, R1 is O-methyl. Preferably, B1 is a pyridyl group substituted with a group selected from: Cl, Br, CN; methyl; and pyridine. Preferably, B1 is a phenyl group substituted with a group selected from: halogen, such as F or Br.

[0372] When A1 is Equation 3, its preferred choice is...

[0373]

[0374] When A1 is

[0375] And when X is S, then R1 is selected from H; OH; OC. 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OCs optionally substituted with one or more halogens. 1-4 Alkyl; or OC substituted with at least one of the following groups. 1-4 Alkyl: phenyl and phenyl substituted with one or more groups selected from OH and halogens, and B1 is selected from pyridyl, which is optionally substituted with groups selected from: Cl; Br; C2-alkynyl; CN; methyl; CF3; pyridine; imidazole; pyrimidine; oxazole; tetrahydrobipyridine; spiroheterocyclic; and thiazole; and phenyl, which is optionally substituted with groups selected from: halogens and C2-substituted with F. 1-3Alkyl. Preferably, R1 is selected from H, OH, methoxy, ethoxy, OCH2CF3, or one to three substituted methoxy groups selected from the group consisting of: phenyl and phenyl substituted with one to three groups selected from OH and halogens. Preferably, B1 is selected from pyridyl, pyridyl substituted with one to three groups selected from: Cl, Br, C2-alkynyl; CN; methyl; CF3; N-(2-oxa)-6-azaspiro[3.3]heptyl; pyridine; imidazole; pyrimidine; oxazole; tetrahydrobipyridine; and thiazole. Preferably, B1 is selected from phenyl substituted with one to three groups selected from: F, Cl, Br, CN and C2-substituted with F. 1-3 alkyl.

[0376] When A1 is

[0377] And when X is S, then R1 is selected from H; OH; OC. 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; OC groups substituted with halogens 1-4 Alkyl; or OC substituted with at least one of the following groups. 1-4 Alkyl groups: phenyl groups and phenyl groups substituted with one or more groups selected from OH and halogens, and B1 is selected from pyridyl groups, which are optionally substituted with groups selected from: Cl; Br; CN; C2-alkynyl; methyl; CF3; pyridine; imidazole; pyrimidine; oxazole; tetrahydrobipyridine; and thiazole; and phenyl groups, which are optionally substituted with groups selected from: halogens, CN, and C2-alkynyl groups optionally substituted with F. 1-3 Alkyl group. Preferably, R1 is selected from H, OH, methoxy, ethoxy, isopropoxy, or OCH2CF3. Preferably, B1 is selected from phenyl groups substituted with one to three groups selected from CN, Cl, Br, or F. Preferably, B1 is selected from pyridine groups substituted with one to three groups selected from CN, Cl, and imidazole.

[0378] When A1 is

[0379] And when X is S, then R1 is selected from OC. 1-4 Alkyl groups, such as O-methyl, O-ethyl, or O-isopropyl; or OC groups substituted with at least one of the following groups. 1-4 Alkyl: phenyl and phenyl groups substituted with one or more groups selected from OH and halogens, and B1 is selected from pyridyl, which is optionally substituted with a group selected from: Cl, Br or CN; C2-alkynyl; methyl; CF3; pyridine; pyrimidine; oxazole; tetrahydrobipyridine; and thiazole. Preferably, R1 is selected from methoxy, ethoxy or isopropoxy, such as methoxy. Preferably, B1 is selected from pyridyl, which is optionally substituted with one to three groups selected from: Cl, Br, CN.

[0380] When A1 is equation 2 and R 2 It is halogen and R 3 Choose C freely 1-6 When the group consists of alkyl groups and halogens and X is S, then R1 is OC. 1-4 Alkyl groups, such as O-methyl, and B1 is a pyridine substituted with groups selected from halogens and CN. In one embodiment, A1 is of formula 2 and R 2 It is Cl, and R 3 Choose from the following groups: methyl and halogen.

[0381] In yet another embodiment, the compound of formula (1) is selected from any of the following:

[0382] 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,

[0383] 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

[0384] 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

[0385] 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

[0386] 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

[0387] 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

[0388] 3,5-Dichloro-4-fluorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside,

[0389] 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-isopropyl-1-thio-α-D-galactopyranoside,

[0390] 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside,

[0391] 3,4-Dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0392] 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

[0393] 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

[0394] 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

[0395] 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

[0396] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-chlorothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0397] 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,

[0398] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0399] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0400] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside

[0401] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0402] 5-Chloro-2-(pyrimidin-5-yl)-pyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0403] 5-Chloro-2-(pyridin-4-yl)-pyridin-3-yl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0404] 5-Chloro-2-(pyridin-3-yl)-pyridin-3-yl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0405] 5-Chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl 3-[4-(2-aminothiazolin-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0406] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside

[0407] 5-Chloro-2-(pyridin-2-yl)-pyridin-3-yl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0408] 5-Chloro-2-(oxazol-2-yl)pyridin-3-yl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0409] 3,4-Dichlorophenyl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0410] 5-Chloro-2-(thiazo-2-yl)pyridin-3-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0411] 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,

[0412] 3-Chlorophenyl 3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0413] 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,

[0414] 3-Bromo-2-trifluoromethylpyridin-5-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0415] 5-Bromo-2-cyanopyridin-3-yl-3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0416] 2-Cyano-5-methylpyridin-3-yl-3-deoxy-3-[4-(4-methyltriazol-2-yl)-1H-1,2,3-thiazo-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0417] 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

[0418] 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,

[0419] 5-Chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptyl}-pyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0420] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0421] 5-Cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0422] 3,5-Dichloro-4-fluorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0423] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside,

[0424] 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,

[0425] 3-Cyano-2-(trifluoromethyl)pyridin-5-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0426] 5-Chloro-2-(N-azacyclobutylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0427] 5-Chloro-2-(pyridin-2-yl)-pyridin-3-yl 3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0428] 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

[0429] 5-Chloropyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0430] 5-Bromopyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0431] 5-Chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0432] 3-Chloro-5-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0433] 3-Chloro-4-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside,

[0434] 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,

[0435] 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,

[0436] 5-Bromo-2-cyanopyridin-3-yl-3-[4-(4,5-dichlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0437] 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

[0438] 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,

[0439] 5-Bromo-2-cyanophenyl-3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0440] 5-Bromo-2-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0441] 5-Bromo-2-(N-methyl-carbonyl)phenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0442] 5-Bromo-2-(N-methyl-carbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0443] 5-Chloro-2-(N-methyl-carbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0444] 5-Bromo-2-cyanophenyl-3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0445] 5-Bromo-2-cyanopyridin-3-yl-3-[4-(5-chloro-4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0446] 5-Bromo-2-cyanophenyl 3-[4-(5-chloro-4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0447] 2,5-Dichlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0448] 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

[0449] 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

[0450] 5-Bromo-2-fluorophenyl 3-deoxy-3-[4-(4-methylthiazolyl-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0451] 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

[0452] 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

[0453] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0454] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0455] 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0456] 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0457] 5-Chloro-2-(pyridin-2-yl)pyridin-3-yl 3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0458] 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

[0459] 3,4-Dichlorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(2,2,2-trifluoroethyl)-1-thio-α-D-galactopyranoside,

[0460] 3,4-Dichlorophenyl 3-deoxy-2-O-(2,2,2-trifluoroethyl)-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside,

[0461] 5-Ethynylpyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0462] 5-Ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0463] 5-Cyanopyridin-3-yl-3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside,

[0464] 5-Cyanopyridin-3-yl-3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0465] 2-Cyano-5-ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0466] 2-Cyano-5-ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0467] 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

[0468] 3,4-Dichlorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside,

[0469] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside,

[0470] 3-Chloro-4-cyanophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0471] 5-Bromo-2-(N,N-dimethylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside,

[0472] 5-Ethynyl-2-(N,N-dimethylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0473] 5-Ethynyl-2-(N-azacyclobutylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0474] 5-Chloro-2-(N-methylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0475] 5-Chloro-2-(N-ethylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0476] 5-Chloro-2-(N-methylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside,

[0477] 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,

[0478] 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,

[0479] 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,

[0480] 5-Cyano-1,3-benzothiazo-6-yl-3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0481] 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

[0482] 5-Methylthioalkylpyridin-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

[0483] 5-(trifluoromethylthioalkyl)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.

[0484] Those skilled in the art will understand that it may be necessary to adjust or change the order of steps in processes a1 to a40, and such changes in order are covered by the aspects of the process and the accompanying descriptions of the process steps as described in the above reaction scheme.

[0485] Furthermore, those skilled in the art should understand that, in the methods described above and below, it may be necessary to protect the functional groups of the intermediate compound with protecting groups.

[0486] The functional groups to be protected include hydroxyl, amino, and carboxylic acids. Suitable protecting groups for hydroxyl groups include optionally substituted and / or unsaturated alkyl groups (e.g., methyl, allyl, benzyl, or tert-butyl), trialkylsilyl or diarylalkylsilyl (e.g., tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or trimethylsilyl), AcO (acetoxy), TBS (tert-butyldimethylsilyl), TMS (trimethylsilyl), PMB (p-methoxybenzyl), and tetrahydropyranyl. Suitable protecting groups for carboxylic acids include (C... 1-6 )-alkyl or benzyl esters. Suitable protecting groups for amino groups include tert-butoxycarbonyl, benzyloxycarbonyl, 2-(trimethylsilyl)-ethoxy-methyl, or 2-trimethylsilylethoxycarbonyl (Teoc). Suitable protecting groups for S include SC(=N)NH2, TIPS.

[0487] The protection and deprotection of functional groups can occur before or after any of the reactions described above.

[0488] Furthermore, those skilled in the art should understand that, in order to obtain the compounds of the present invention in an alternative and, in some cases, more convenient manner, the individual process steps mentioned above may be carried out in a different order, and / or the individual reactions may be carried out at different stages throughout the route (i.e., substituents may be added to and / or chemically transformed into those different intermediates mentioned above in conjunction with specific reactions). This may not require or necessitate the use of protecting groups.

[0489] In yet another embodiment, compound (1) is in a free form. As used herein, “in a free form” means that the compound of formula (1) is in an acidic or basic form, or as a neutral compound, depending on the substituents. Furthermore, the free form does not contain any acidic or basic salts. In one embodiment, the free form is an anhydrous compound. In another embodiment, the free form is a solvate, such as a hydrate.

[0490] In yet another embodiment, the compound of formula (1) is in crystalline form. Those skilled in the art can perform tests to identify polymorphs, and such polymorphs are intended to be covered by the term "crystalline form" as used herein.

[0491] When the compounds and pharmaceutical compositions disclosed herein are used for the above treatment, a therapeutically effective amount of at least one compound is administered to the mammal in need of the treatment.

[0492] As used in this article, the term "C" 1-x "Alkyl" refers to an alkyl group containing 1-x carbon atoms, such as C 1-5 Or C 1-6 Such as methyl, ethyl, propyl, butyl, pentyl or hexyl.

[0493] As used in this article, the term "branch C" 3-6 "Alkyl" refers to branched alkyl groups containing 3-6 carbon atoms, such as isopropyl, isobutyl, tert-butyl, isopentyl, 3-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 2,2-dimethylbutyl, and 2,3-dimethylbutyl.

[0494] As used in this article, the term "C" 3-7 "Cycloalkyl" refers to cyclic alkyl groups containing 3 to 7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and 1-methylcyclopropyl.

[0495] As used in this article, the term "C" 5-7 "Cycloalkyl" refers to a cyclic alkyl group containing 5-7 carbon atoms, such as cyclopentyl, cyclohexyl, or cycloheptyl.

[0496] As used in this article, the term "C2-alkynyl" refers to -CCH, where the two carbons are linked by a triple bond.

[0497] As used in this article, the term "oxo" refers to an oxygen atom with a double bond, also indicated as =O.

[0498] As used in this article, the term "CN" refers to nitrile.

[0499] As used herein, the term "five-membered or six-membered heteroaromatic ring" refers to either a five-membered or a six-membered heteroaromatic ring. A five-membered heteroaromatic ring contains five ring atoms, one to four of which are heteroatoms selected from N, O, and S. A six-membered heteroaromatic ring contains six ring atoms, one to five of which are heteroatoms selected from N, O, and S. Examples include thiophene, furan, pyran, pyrrole, imidazole, pyrazole, isothiazol, isoxazol, pyridine, pyrazine, pyrimidine, and pyridazine. When such heteroaromatic rings are substituents, they are referred to as thiophene, furanyl, pyranyl, pyrroleyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, pyridinyl, pyrazinyl, pyrimidinyl, and pyridazinyl. Also included are oxazolyl, thiazolyl, thiadiazolyl, oxadiazolyl, and pyridinoneyl.

[0500] As used herein, the term "heterocycle, such as heteroaryl or heterocycloalkyl" means a heterocycle consisting of one or more 3- to 7-membered ring systems containing one or more heteroatoms, wherein such ring systems may optionally be aromatic. As used herein, the term "heteroaryl" means a monocyclic or bicyclic aromatic ring system containing one or more heteroatoms selected from O, S, and N (such as 1 to 10, for example 1 to 6), including but not limited to benzothiazolyl, oxazolyl, oxadiazolyl, thienyl, thiadiazolyl, thiazolyl, thiazopyridyl, pyridyl, pyridinyl, pyridonel, pyrimidinyl, quinolinyl, azaquinolinyl, isoquinolinyl, azaisoquinolinyl, quinazolinyl, azaquinazolinyl, benzoxazolyl, azabenzoxazolyl, benzothiazolyl, or azabenzothiazolyl. As used herein, the term "heterocyclic alkyl" means a monocyclic or bicyclic 3-7 membered aliphatic heterocycle containing one or more heteroatoms selected from O, S, and N (such as 1 to 7, e.g., 1 to 5), including but not limited to nitrogen-containing heterocyclic butyl, piperidinyl, tetrahydropyranyl, tetrahydrothiaranyl, or piperidinoneyl.

[0501] 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). The terms are intended to encompass a full spectrum of treatment for a given condition suffered by a patient, such as the administration of active compounds to alleviate symptoms or complications, delay the progression of the disease, disorder, or symptom, reduce or alleviate symptoms and complications, and / or cure or eliminate the disease, disorder, or symptom, as well as prevention of the condition, wherein prevention is understood as the management and care of a patient for the purpose of combating a disease, symptom, or disorder and includes the administration of active compounds to prevent the onset of symptoms or complications. Treatment can be administered in a short-term or long-term manner. Patients to be treated are preferably mammals; particularly humans, but may also include animals such as dogs, cats, cattle, sheep, and pigs.

[0502] As used herein, the term "therapeutic effective amount" for compounds of formula (1) of this invention means an amount sufficient to cure, alleviate, or partially prevent the clinical manifestations of a given disease and its complications. An amount sufficient to achieve this is defined as a "therapeutic effective amount." The effective amount for each purpose will depend on the severity of the disease or injury, as well as the subject's weight and general condition. It should be understood that the appropriate dosage can be determined using routine experiments by constructing a matrix of values ​​and testing the differences in the matrix, all within the general skill of a trained physician or veterinarian.

[0503] In yet another aspect, the present invention relates to a pharmaceutical composition comprising a compound of formula (1) and optionally pharmaceutically acceptable additives, such as carriers or excipients.

[0504] As used herein, “pharmaceuticalally acceptable additives” means, but is not limited to, carriers, excipients, diluents, adjuvants, colorants, fragrances, preservatives, etc., which are considered by those skilled in the art when formulating the compounds of the present invention to manufacture pharmaceutical compositions.

[0505] The adjuvants, diluents, excipients, and / or carriers that can be used in the compositions of the present invention must be pharmaceutically acceptable in terms of compatibility with the compounds of formula (1) and other components of the pharmaceutical composition, and must be harmless to their receptors. Preferably, the compositions should not contain any materials that may 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.

[0506] As mentioned above, in addition to the compounds disclosed herein, the compositions disclosed herein, and particularly pharmaceutical compositions, may further comprise at least one pharmaceutically acceptable adjuvant, diluent, excipient, and / or carrier. In some embodiments, the pharmaceutical composition comprises from 1% to 99% by weight of the at least one pharmaceutically acceptable adjuvant, diluent, excipient, and / or carrier, and from 1% to 99% by weight of the compound disclosed herein. The combined amount of the active ingredient and the pharmaceutically acceptable adjuvant, diluent, excipient, and / or carrier may not exceed 100% by weight of the composition, particularly the pharmaceutical composition.

[0507] In some implementations, for the purposes discussed above, only one compound as disclosed herein is used.

[0508] In some implementations, two or more compounds as disclosed herein are used in combination for the purposes discussed above.

[0509] Compositions containing the compounds described herein, particularly pharmaceutical compositions, may be suitable for oral, intravenous, topical, intraperitoneal, nasal, buccal, sublingual, or subcutaneous administration, or for administration via the respiratory tract, in the form of, for example, aerosols or air-suspended fine powders. Therefore, pharmaceutical compositions may be in the form of, for example, tablets, capsules, powders, nanoparticles, crystals, amorphous substances, solutions, transdermal patches, or suppositories.

[0510] Further implementations of the method are described in the experimental section of this document, and each individual method and each starting material constitutes an implementation that can form part of the implementation.

[0511] The above embodiments should be construed as referring to any aspect described herein (such as 'treatment method', 'pharmaceutical composition', 'compound used as a pharmaceutical agent' or 'compound used in a method') and any embodiment described herein, unless an embodiment is specified to relate to one or more aspects of the invention.

[0512] All references cited in this article (including publications, patent applications and patents) are hereby incorporated by reference to the extent that each reference is individually and specifically indicated to be incorporated by reference and presented in its entirety in this article.

[0513] All headings and subheadings used herein are for convenience only and should not be construed as limiting the invention in any way.

[0514] Unless otherwise indicated herein or otherwise expressly contradicted in the context, the invention includes any combination of the foregoing elements in all its possible variations.

[0515] Unless otherwise indicated herein or explicitly contradicted by the context, the terms “a”, “an”, and “the” as used in the context of describing the invention, and similar pronouns, shall be interpreted to include both the singular and the plural.

[0516] Unless otherwise indicated herein, the enumeration of numerical ranges herein is intended only as a concise method of individually referring to each individual value falling within the range, and each individual value is incorporated into this specification as if it were individually enumerated herein. Unless otherwise stated, all exact values ​​provided herein represent corresponding approximations (e.g., all exact exemplary values ​​provided with respect to a particular factor or measurement may be considered to also provide corresponding approximate measurements, modified with “about” where appropriate).

[0517] All methods described herein may be performed in any suitable order unless otherwise indicated herein or explicitly contradicted by the context.

[0518] The use of any and all embodiments or exemplary language (e.g., “such as”) provided herein is intended only to better illustrate the invention and does not constitute a limitation on the scope of the invention, unless otherwise indicated. No language in the specification should be construed as indicating that any element is necessary for the practice of the invention, unless explicitly stated otherwise.

[0519] The references and inclusions of patent literature in this document are for convenience only and do not reflect any view on the validity, patentability and / or enforceability of such patent literature.

[0520] As used herein, the term "and / or" is intended to refer both to two alternatives and to each alternative individually. For example, the expression "xxx and / or yyy" means "xxx and yyy"; "xxx"; or "yyy", all three alternatives being subject to individual implementation schemes.

[0521] Unless otherwise stated or explicitly contradicted by the context, the use of terms such as “comprising,” “having,” “including,” or “containing” in relation to one or more elements in the description of any aspect or embodiment of the invention is intended to provide support for similar aspects or embodiments of the invention that are “consisting of,” “substantially composed of,” or “substantially contain” the specific elements (e.g., unless otherwise stated or explicitly contradicted by the context, a composition described herein as comprising a specific element should be understood to also describe a composition comprising that element). The invention includes all modifications and equivalents to the subject matter set forth in the various aspects or claims presented herein, to the fullest extent permitted by applicable law.

[0522] The invention is further illustrated by the following embodiments; however, these embodiments should not be construed as limiting the scope of protection. The features disclosed in the foregoing description and in the following embodiments can (alone and in any combination thereof) be substantial for implementing the invention in its various forms.

[0523] Experimental Procedure (Evaluation of Kd Value)

[0524] The affinity of Examples 1-103 for galactolectin was determined by fluorescence anisotropy assay, wherein the compounds described therein were used as inhibitors of the interaction between galactolectin and fluorescein-labeled sugar probes as described below: P., Kahl-Knutsson, B., Huflejt, M., Nilsson, UJ and Leffler H. (2004) Fluorescence polarization as an analytical tool to evaluate galectin-ligandinteractions. Anal.Biochem.334:36-47,( et al., 2004) and Monovalent interactions of Galectin-1, Salomonsson, Emma; Larumbe, Amaia; Tejler, Johan; Tullberg, Erik; Rydberg, Hanna; Sundin, Anders; Khabut, Areej; Frejd, Torbjorn; Lobsanov, Yuri D.; Rini, James M.; et al., From Biochemistry (2010), 49(44), 9518-9532, (Salomonsson et al., 2010).

[0525]

[0526]

[0527]

[0528]

[0529]

[0530]

[0531]

[0532]

[0533]

[0534]

[0535]

[0536]

[0537]

[0538]

[0539]

[0540]

[0541]

[0542]

[0543]

[0544]

[0545]

[0546] For some compounds of the present invention, wherein R of formula 1 1 Alkylated hydroxyl groups, such as -OCH3, were observed to have high uptake and no efflux in a CACO-2 model of uptake via the human gut. This suggests a high probability of high oral bioavailability in humans. (See Artursson, P.; Ungelll, A.-L.;) 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 shows a Papp from the top side to the outer side of the basolateral layer (A>B) of 20*10^-6 cm / s and a Papp from the outer side of the basolateral layer to the top side (B>A) of 28*10^-6 cm / s. This means that the uptake is very high and almost no efflux is observed.

[0547] Examples and synthesis of intermediates

[0548] General Experiment:

[0549] Nuclear magnetic resonance (NMR) spectra were recorded at 400 MHz and 25 °C on a Bruker AVANCE III 500 instrument or a Varian instrument.

[0550] Residual solvent was used as an internal standard, and chemical shifts were reported in ppm(d). Peak multiplicity was expressed as follows: s, singlet; d, doublet; dd, twin doublet; t, triplet; dt, twin triplet; q, quartet; m, multiplet; br s, broad singlet. In the case of angioparticle mixtures, the shifts of individual angioparticles were reported separately, and the α / β ratio was calculated based on the integral of the angioparticle peaks.

[0551] LC-MS was obtained on an Agilent 1200 HPLC coupled to an Agilent MSD mass spectrometer, operating in ES(+) ionization mode. Column: 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 was obtained on an Agilent 1100 HPLC coupled to an Agilent MSD mass spectrometer, operating in ES(+) ionization mode. Column: Waters Symmetry 2.1 x 30 mm C18 or Chromolith RP-18 2 x 50 mm. Solvent A: water + 0.1% TFA and Solvent B: acetonitrile + 0.1% TFA. Wavelength: 254 nm.

[0552] Preparative HPLC was performed on a Gilson 281. Flow rate: 20 mL / min, column: X-Select 10 μm 19 × 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 × 250 mm) column. Wavelength: 254 nm. Solvent A: water (10 mM ammonium bicarbonate) and solvent B: acetonitrile. Alternatively, preparative HPLC was performed 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.

[0553] Use the following abbreviations

[0554] aq: water-based

[0555] Calcd: Calculated value

[0556] MeCN: Acetonitrile

[0557] CuI: Copper Iodide

[0558] DCM: Dichloromethane

[0559] DIPEA: Diisopropylethylamine

[0560] DMF: N,N-Dimethylformamide

[0561] ESI-MS: Electrospray ionization mass spectrometry

[0562] EtOAc or EA: Ethyl acetate

[0563] Et3N: Triethylamine

[0564] GC: Gas Chromatography

[0565] h: hours

[0566] HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate

[0567] HPLC: High Performance Liquid Chromatography

[0568] LC: Liquid Chromatography

[0569] MeCN: Acetonitrile

[0570] mL: milliliters

[0571] MeOH: Methanol

[0572] MeOD: Deuterated methanol

[0573] mm: millimeter

[0574] mM: millimoles

[0575] MS: Mass spectrometry

[0576] nm: nanometer

[0577] NaI: Sodium iodide

[0578] NaOMe: Sodium methoxide

[0579] N2: Nitrogen gas

[0580] NMR: Nuclear Magnetic Resonance

[0581] Pd(PPh3)4: Tetra(triphenylphosphine)palladium(0)

[0582] PE: Petroleum ether

[0583] pH: Acidity

[0584] Prep: Preparative

[0585] rt: room temperature

[0586] TBAF: Tetrabutylammonium fluoride

[0587] TFA: Trifluoroacetic acid

[0588] THF: Tetrahydrofuran

[0589] TMS: Trimethylsilyl

[0590] UV: Ultraviolet

[0591] Angstrom

[0592] Examples 1-103 were synthesized from their corresponding intermediates 1-103.

[0593] Example 1

[0594] 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

[0595]

[0596] TFA (0.5 mL, 6.73 mmol) and H2O (0.5 mL) were added to a solution of 3,5-dichloro-4-fluorophenyl-4,6-O-benzyl-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). The mixture was stirred at room temperature for 12 h. Et3N (2.0 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, UV 254] to give the title compound (54 mg, 84%). ESI-MS m / z, for [C 18 H 17 Cl2FN4O4S2][M+H] + Calculated value: 507.0; Measured value: 507.0. 1 H NMR (400MHz, methanol-d4) δ8.50(s,1H),7.79(d,J=3.2Hz,1H),7.66(d,J=6.0Hz,2H),7.54(d,J=3.2,1H),6.08(d,J=5.2Hz,1H),4.95 (dd,J=11.2,2.8Hz,1H),4.52(dd,J=11.2,5.2Hz,1H),4.39-4.36(m,1H),4.10(d,J=2.4Hz,1H),3.62-3.60(m,2H),3.31(s,3H).

[0597] Example 2

[0598] 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

[0599]

[0600] A solution of 5-bromopyridin-3-yl 4,6-O-benzyl-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 room temperature for 2 h. A saturated aqueous solution of NaHCO3 was added dropwise to adjust the pH to 7–8. Water (10 mL) and DCM (15 mL) were added, and the phases were separated. The separated aqueous phase was further extracted with DCM (2 x 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 provide the title compound (90 mg, 63%). ESI-MS m / z, for [C 17 H 18 BrN5O4S2][M+H] + Calculated value: 500.0, Measured value: 500.0 1 H NMR (400MHz, methanol-d4) δ8.60(d,J=1.8Hz,1H),8.51(s,1H),8.48(d,J=2.1Hz,1 H),8.26(t,J=2.0Hz,1H),7.80(d,J=3.3Hz,1H),7.55(d,J=3.3Hz,1H),6.18( d,J=5.3Hz,1H),4.99(dd,J=11.4,2.9Hz,1H),4.55(dd,J=11.4,5.3Hz,1H), 4.37(t,J=5.9Hz,1H), 4.11(d,J=1.9Hz,1H), 3.63-3.52(m,2H), 3.32(s,3H).

[0601] Example 3

[0602] 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

[0603]

[0604] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-deoxy-2-O-methyl-3-[4-(thiazolyl-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), Et3N (2.0 mL), and water (1.0 mL) was stirred at room temperature for 4 h. The mixture was 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 provide the title compound (22.0 mg, 45%). ESI-MS m / z, for [C 18 H 17 BrN6O4S2][M+H] + Calculated value: 525.0, measured value: 525.0. 1 H NMR (400MHz, methanol-d4) δ8.73(d,J=2.0Hz,1H),8.65(d,J=2.0Hz,1H),8.64(s,1H),7.91(d,J=3.6Hz,1H),7.66(d,J=3.2Hz,1H),6.53(d,J=5.2Hz,1 H), 5.16 (dd, J = 11.2, 2.8Hz, 1H), 4.74 (dd, J = 11.2, 5.2Hz, 1H), 4.43 (t, J = 6.0Hz, 1H), 4.24 (d, J = 2.4Hz, 1H), 3.70 (d, J = 6.0Hz, 2H), 3.40 (s, 3H).

[0605] Example 4

[0606] 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

[0607]

[0608] A solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzyl-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 room temperature for 1 h. The pH of the mixture was adjusted to approximately 8 using Et3N, and the solvent was then evaporated. 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, UV 254) to give the title compound (40.5 mg, 53%). ESI-MS m / z, for [C 18 H 17 ClN6O4S2][M+H] + Calculated value: 481.0, measured value: 481.0. 1 H NMR (400MHz, methanol-d4) δ8.56-8.47(m,2H),8.38(d,J=2.1Hz,1H),7.80(d,J=3.3Hz,1H),7.55(d,J=3.3Hz,1H),6.42(d,J=5.3Hz,1H),5. 04(dd,J=11.3,2.8Hz,1H),4.62(dd,J=11.3,5.3Hz,1H),4.31(t,J=6.0Hz,1H),4.13(d,J=2.4Hz,1H),3.66-3.52(m,2H),3.37(s,3H).

[0609] Example 5

[0610] 5-Chloro-2-cyanopyridin-3-yl2-O-benzyl-3-deoxy-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0611]

[0612] A solution of 5-chloro-2-cyanopyridin-3-yl-2-O-benzyl-4,6-O-benzyl-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 room temperature for 3 h. The mixture was neutralized with Et3N 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, UV 254] to give the title compound (23.3 mg, 40%). ESI-MS m / z, for [C 24 H 21 ClN6O4S2][M+H] + Calculated value: 557.1; Measured value: 557.0. 1 H NMR (400MHz, DMSO-d6) δ8.75(d,J=2.0Hz,1H),8.69(s,1H),8.56(d,J=2.0Hz,1H),7.95 (d,J=3.2Hz,1H),7.80(d,J=3.2Hz,1H),7.26-7.16(m,3H),7.16-7.07(m,2H),6.69(d, J=5.2Hz,1H),5.67(d,J=6.0Hz,1H),5.01(ddd,J=16.8,11.2,4.0Hz,2H),4.86-4.72(m ,2H),4.54(d,J=11.2Hz,1H),4.31-4.20(m,1H),4.15-4.06(m,1H),3.59-3.39(m,2H).

[0613] Example 6

[0614] 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

[0615]

[0616] TFA (502 mg, 4.4 mmol) and H2O (0.5 mL) were added to a solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzyl-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), and the mixture was stirred at room temperature for 12 h. Et3N (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, UV 254] to give the title compound (30 mg, 34%). ESI-MS m / z, for [C 24 H 19 ClF2N6O5S2][M+H] + Calculated value: 609.1; Measured value: 609.1. 1 H NMR (400MHz, methanol-d4) δ8.51(d,J=2.0Hz,1H),8.39-8.37(m,1H),8.34(d,J=2.0H z,1H),7.80(d,J=3.2Hz,1H),7.54(d,J=3.6Hz,1H),6.59-6.50(m,2H),6.30(d, J=5.6Hz,1H),5.08(dd,J=11.2,2.8Hz,1H),4.73(dd,J=11.2,5.6Hz,1H),4.56 (d,J=11.6Hz,1H),4.35-4.29(m,2H),4.12(d,J=2.8Hz,1H),3.60-3.58(m,2H).

[0617] Example 7

[0618] 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

[0619]

[0620] A solution of 3,5-dichloro-4-fluorophenyl 4,6-O-benzyl-3-deoxy-3-[4-(2-hydroxythiazo-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 room temperature for 3 h. Et3N 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, for [C 18 H 17 Cl2FN4O5S2][M+H] + Calculated value: 523.0; Measured value: 523.0. 1 H NMR (400MHz, methanol-d4) δ8.35(s,1H),7.74(d,J=6.3Hz,2H),6.70(s,1H),6.16(d,J=5.3Hz,1H),4.99(dd,J=11.4,2.8 Hz, 1H), 4.53 (dd, J = 11.4, 5.3Hz, 1H), 4.45 (t, J = 6.0Hz, 1H), 4.16 (d, J = 2.4Hz, 1H), 3.75-3.61 (m, 2H), 3.38 (s, 3H).

[0621] Example 8

[0622] 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

[0623]

[0624] DIPEA (0.138 mL, 0.81 mmol) was added to a solution of 3,4-dichlorophenyl-3-azido-4,6-O-benzyl-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), followed by the addition of CsF (49 mg, 0.32 mmol) and CuI (9.21 mg, 0.048 mmol), and the mixture was stirred at room temperature for 4 h. The mixture was diluted with water (5 mL) and extracted with DCM. The organic phase was washed with water (6 x 5 mL) and concentrated. The residue was stirred in DCMTFA (5.25 mL, 20:1) at room temperature 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, UV 254) to give the title compound (10.1 mg, 12%). ESI-MS m / z, for [C 20 H 22 Cl2N4O5S2][M+H] + Calculated value: 533.0, measured value: 533.0. 1 H NMR (400MHz, methanol-d4) δ8.30(s,1H),7.68(d,J=1.9Hz,1H),7.41(dt,J=16.1,5 .2Hz,2H),6.61(s,1H),6.00(d,J=5.3Hz,1H),4.91(dd,J=11.3,2.8Hz,1H), 4.60(dd,J=11.3,5.3Hz,1H),4.51(s,1H),4.33(t,J=6.2Hz,1H),4.08(d,J= 2.4Hz, 1H), 3.71-3.51 (m, 3H), 1.02 (d, J = 6.1Hz, 3H), 0.77 (d, J = 6.0Hz, 3H).

[0625] Example 9

[0626] 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

[0627]

[0628] TFA (1.46 g, 12.8 mmol) and H2O (0.5 mL) were added to a solution of 3,4-dichlorophenyl 4,6-O-benzyl-3-deoxy-3-[4-(2-hydroxythiazo-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), and the mixture was stirred at room temperature for 12 h. Et3N (3.0 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, UV 254] to give the title compound (90 mg, 70%). ESI-MS m / z, for [C 18 H 18 Cl2N4O5S2][M+H] + Calculated value: 505.0; Measured value: 504.8. 1 H NMR (400MHz, methanol-d4) δ8.38(s,1H),7.84(d,J=2.0Hz,1H),7.56-7.50(m,2H),6.73(s,1H),6.19(d,J=5.6Hz,1H),5.03(dd,J =11.2, 2.8Hz, 1H), 4.56 (dd, J = 11.2, 5.2Hz, 1H), 4.49-4.46 (m, 1H), 4.19 (d, J = 2.0Hz, 1H), 3.74-3.67 (m, 2H), 3.40 (s, 3H).

[0629] Example 10

[0630] 3,4-Dichlorophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0631]

[0632] To a solution of 4,6-di-O-acetyl-3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-D-galactosene (25 mg, 0.066 mmol) and oxotrichloro[(dimethyl sulfide)triphenylphosphine oxide]rhenium (V) (4.3 mg, 0.0066 mmol) in toluene (1 mL), 3,4-dichlorobenzenethiol (13 μL, 0.099 mmol) was added and the mixture was stirred at 70 °C for 20 h. The mixture was evaporated and the residue was stirred at room temperature for 30 min in NaOMe (0.1 mL, 1 M) and MeOH (0.5 mL). The solution was concentrated and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA) to provide the title compound (1.02 mg, 3%). ESI-MS m / z, for [C 17 H 16 Cl2N4O4S2][M+H] + Calculated value: 475.0; Measured value: 475.0 1 H NMR (400MHz, methanol-d4) δ8.29(s,1H),7.78(d,J=1.9Hz,1H),7.51(dd,J=8.4,2.0Hz,1H),7.48(d,J=8.4Hz,1H),6.68(s,1H),5.93(d,J=5.5Hz ,1H),5.19-5.12(m,1H),4.47(t,J=6.1Hz,1H),4.16(s,1H),3.78-3.68(m,2H),3.09(td,J=13.6,5.9Hz,1H),2.32(dd,J=13.3,4.1Hz,1H).

[0633] Example 11

[0634] 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

[0635]

[0636] 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), Et3N (3.0 mL), and water (1.0 mL) was stirred at room temperature for 3 h. 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, UV 254) to give the title compound (10.3 mg, 42%). ESI-MS m / z, for [C 18 H 16 BrClN6O4S2][M+H] + Calculated value: 559.0; Measured value: 558.9. 1 H NMR (400MHz, methanol-d4) δ8.73(d,J=2.0Hz,1H),8.67(s,1H),8.65(d,J=2.0Hz,1H),7.50(s,1H),6.53(d,J=5.2Hz,1H),5.16(dd,J= 11.2, 3.2Hz, 1H), 4.73 (dd, J = 11.2, 5.6Hz, 1H), 4.43 (t, J = 6.0Hz, 1H), 4.24 (d, J = 2.4Hz, 1H), 3.70 (d, J = 6.0Hz, 2H), 3.49 (s, 3H).

[0637] Example 12

[0638] 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

[0639]

[0640] A solution of 3-bromo-2-cyanopyridin-5-yl4,6-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), Et3N (2.0 mL), and water (1.0 mL) was stirred at room temperature for 3 h. 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, UV 254) to give the title compound (13.3 mg, 44%). ESI-MS m / z, for [C 18 H 16 BrClN6O4S2][M+H] + Calculated value: 559.0; Measured value: 559.0. 1 H NMR (400MHz, methanol-d4) δ8.80(d,J=2.0Hz,1H),8.67(s,1H),8.53(d,J=2.0Hz,1H),7.49(s,1H),6.58(d,J=5.6Hz,1H),5.14(dd,J= 11.6, 2.8Hz, 1H), 4.74 (dd, J = 11.6, 5.2Hz, 1H), 4.35 (t, J = 6.0Hz, 1H), 4.20 (d, J = 2.4Hz, 1H), 3.70 (d, J = 6.0Hz, 2H), 3.42 (s, 3H).

[0641] Example 13

[0642] 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

[0643]

[0644] A solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzyl-3-[4-(4-chloro-thiazo-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 room temperature for 1 h, and then the pH was adjusted to pH 8 with Et3N. The mixture was concentrated and purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3) = 20%–70%, X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to give the title compound (25.0 mg, 42%). ESI-MS m / z, for [C 18 H 16 Cl2N6O4S2][M+H] + Calculated value: 515.0, measured value: 515.0. 1 H NMR (400MHz, methanol-d4) δ8.55(s,1H),8.50(d,J=2.1Hz,1H),8.38(d,J=2.1Hz,1H),7.37(s,1H),6.41(d,J=5.3Hz,1H),5.04(dd,J=1 1.3, 2.8Hz, 1H), 4.63 (dd, J = 11.3, 5.3Hz, 1H), 4.31 (t, J = 6.0Hz, 1H), 4.12 (d, J = 2.3Hz, 1H), 3.58 (t, J = 10.3Hz, 2H), 3.37 (s, 3H).

[0645] Example 14

[0646] 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

[0647]

[0648] A solution of 3-chloro-2-cyanopyridin-3-yl4,6-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), Et3N (2.0 mL), and water (1.0 mL) was stirred at room temperature for 3 h. 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, UV 254) to give the title compound (24.5 mg, 59%). ESI-MS m / z, for [C 18 H 16 Cl2N6O4S2][M+H] + Calculated value: 515.0; Measured value: 515.1. 1 H NMR (400MHz, methanol-d4) δ8.76(d,J=2.0Hz,1H),8.67(s,1H),8.40(d,J=1.6Hz,1H),7.49(s,1H),6.59(d,J=5.6Hz,1H),5.14(dd,J =11.2, 2.8Hz, 1H), 4.74 (dd, J = 11.2, 5.2Hz, 1H), 4.35 (t, J = 6.0Hz, 1H), 4.20 (d, J = 2.0Hz, 1H), 3.70-3.72 (m, 2H), 3.42 (s, 3H).

[0649] Example 15

[0650] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-chlorothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0651]

[0652] A solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzyl-3-[4-(2-chlorothiazo-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 room temperature for 1 h. The mixture was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the title compound (28.5 mg, 61%). ESI-MS m / z, for [C 18 H 16 Cl2N6O4S2][M+H] + Calculated value: 515.0; Measured value: 515.0. 1 H NMR (400MHz, methanol-d4) δ8.51(d,J=2.0Hz,1H),8.38(d,J=2.0Hz,1H),8.36(s,1H),7.77(s,1H),6.42(d,J=5.2Hz,1H),5.00(dd,J =11.2, 2.8Hz, 1H), 4.61 (dd, J = 11.2, 5.2Hz, 1H), 4.31 (t, J = 6.0Hz, 1H), 4.11 (d, J = 2.4Hz, 1H), 3.64-3.48 (m, 2H), 3.36 (s, 3H).

[0653] Example 16

[0654] 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

[0655]

[0656] TFA (0.263 mL, 3.54 mmol) was added to a solution of 3,5-dichloro-4-fluorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (54.0 mg, 0.089 mmol) in DCM (5 mL) and the mixture was stirred overnight at room temperature. The mixture was evaporated and purified by column chromatography (MeCN / H2O = 0 / 100-1 / 5, C-18 column, 20 mL / min, UV 254) to provide the title compound (17.9 mg, 39%). ESI-MS m / z, for [C 18 H 18 Cl2FN5O4S2][M+H] + Calculated value: 522.0; Measured value: 522.0. 1 H NMR (400MHz, methanol-d4) δ8.23(s,1H),7.75(d,J=6.3Hz,2H),6.95(s,1H),6.16(d,J=5.3Hz,1H),4.97(dd,J=11.3 ,2.6Hz,1H),4.55(dd,J=11.4,5.3Hz,1H),4.45(t,J=6.2Hz,1H),4.17(s,1H),3.77-3.63(m,2H),3.38(s,3H).

[0657] Example 17

[0658] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0659]

[0660] A solution of 5-chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-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 room temperature for 3 h, and then the pH was adjusted to 8 using Et3N. The mixture was concentrated and purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3) = 0–60%, X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to give the title compound (26.4 mg, 42%). ESI-MS m / z, for [C18 H 18 ClN7O4S2][M+H] + Calculated value: 496.1, measured value: 496.0. 1 H NMR (400MHz, methanol-d4) δ8.50(d,J=2.2Hz,1H),8.38(d,J=2.2Hz,1H),8.16(s,1H),6.87(s,1H),6.41(d,J=5.3Hz,1H),4.96(dd,J=11.3, 2.9Hz, 1H), 4.56 (dd, J = 11.3, 5.3Hz, 1H), 4.29 (t, J = 6.0Hz, 1H), 4.09 (d, J = 2.5Hz, 1H), 3.58 (d, J = 6.1Hz, 2H), 3.37 (d, J = 12.0Hz, 3H).

[0661] Example 18

[0662] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0663]

[0664] TFA (820 mg, 7.19 mmol) and H2O (0.5 mL) were added to a solution of 5-chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (85 mg, 0.14 mmol) in DCM (10 mL), and the mixture was stirred at room temperature for 12 h. Et3N (3.0 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, UV 254] to give the title compound (25 mg, 36%). ESI-MS m / z, for [C 18 H 21 ClN6O4S2][M+H] + Calculated value: 485.1; Measured value: 485.0. 1H NMR (400MHz, methanol-d4) δ8.30(d,J=2.4Hz,1H),8.26(s,1H),8.20(d,J=2.4Hz,1H),6.97(s,1H),6.30(d,J=5.2Hz,1H),5.06(dd,J= 11.6, 2.8Hz, 1H), 4.73-4.56 (m, 1H), 4.39 (t, J = 6.4Hz, 1H), 4.19 (d, J = 2.4Hz, 1H), 3.82-3.58 (m, 2H), 3.40 (s, 3H), 2.66 (s, 3H).

[0665] Example 19

[0666] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside

[0667]

[0668] A solution of 5-chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-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 room temperature for 3 h. The mixture was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the title compound (17.8 mg, 21%). ESI-MS m / z, for [C 24 H 22 ClN7O4S2][M+H] + Calculated value: 572.1; Measured value: 572.2. 1H NMR (400MHz, methanol-d4) δ8.61(d,J=2.4Hz,1H),8.42(d,J=2.4Hz,1H),8.12(s,1H),7.24-7.09(m,5H),6.97(s,1H),6.36(d,J=5.2Hz,1H),5.12(d d,J=11.2,2.8Hz,1H),4.82-4.71(m,2H),4.63(s,1H),4.51(d,J=11.2H z, 1H), 4.41 (t, J = 6.0Hz, 1H), 4.20 (d, J = 2.4Hz, 1H), 3.72-3.63 (m, 2H).

[0669] Example 20

[0670] 5-Chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0671]

[0672] TFA (860 mg, 7.54 mmol) and H2O (0.5 mL) were added to a solution of 5-chloro-2-methylpyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside (115 mg, 0.15 mmol) in DCM (10 mL), and the mixture was stirred at room temperature for 12 h. Et3N (3.0 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, UV 254] to give the title compound (42 mg, 56%). ESI-MS m / z, for [C 19 H 23 ClN6O4S2][M+H] + Calculated value: 499.1; Measured value: 499.0. 1H NMR (400MHz, methanol-d4) δ8.30(d,J=2.4Hz,1H),8.26(s,1H),8.18(d,J=2.4Hz,1H),6.97(s,1H),6.26(d,J=5.2Hz,1H),5.07(dd,J=11.6,2.8Hz,1H), 4.70(dd,J=11.6,5.3Hz,1H),4.48-4.33(m,1H),4.20(d,J=2.4Hz,1H),3 .84-3.61(m,3H),3.51-3.35(m,1H),2.65(s,3H),1.03(t,J=7.0Hz,3H).

[0673] Example 21

[0674] 5-Chloro-2-(pyrimidin-5-yl)pyridin-3-yl3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0675]

[0676] A solution of 5-chloro-2-(pyrimidin-5-yl)pyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-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 room temperature for 1 h. The mixture was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the title compound (27 mg, 45%). ESI-MS m / z, for [C 21 H 21 ClN8O4S2][M+H] + Calculated value: 549.1; Measured value: 549.1. 1H NMR (400MHz, methanol-d4) δ9.13(s,1H),9.06(s,2H),8.54(d,J=2.0Hz,1H),8.36(d,J=2.0Hz,1H),8.11(s,1H),6.85(s,1H),6.00(d, J=4.8Hz,1H),4.80-4.70(s,1H),4.41(d,J=5.6Hz,1H),4.13(t,J=5.6Hz,1H),4.01(s,1H),3.56(d,J=6.0Hz,2H),3.07(s,3H).

[0677] Example 22

[0678] 5-Chloro-2-(pyridin-4-yl)pyridin-3-yl3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0679]

[0680] TFA (0.409 mL, 5.50 mmol) was added to a solution of 5-chloro-2-(pyridin-4-yl)pyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (70.0 mg, 0.11 mmol) in DCM (10 mL) and the mixture was stirred at room temperature for 2 h. Et3N (1 mL) was added 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, UV 254] to provide the title compound (33.0 mg, 55%). ESI-MS m / z, for [C 22 H 22 ClN7O4S2][M+H] + Calculated value: 548.1; Measured value: 547.9. 1¹H NMR (400MHz, 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).

[0681] Example 23

[0682] 5-Chloro-2-(pyridin-3-yl)pyridin-3-yl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0683]

[0684] A solution of 5-chloro-2-(pyridin-3-yl)pyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-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 room temperature for 3 h and then neutralized with Et3N. 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 (32.8 mg, 56%). ESI-MS m / z, for [C 22 H 22 ClN7O4S2][M+H] + Calculated value: 548.1; Measured value: 548.2. 1H NMR (400MHz, DMSO-d6) δ8.83(s,1H),8.65(d,J=2.4Hz,2H),8.41(d,J=1.6Hz,1H),8.11 -8.05(m,2H),7.56(q,J=7.6,4.8Hz,1H),7.07(s,2H),6.89(s,1H),6.27(d,J=5.2Hz,1H ),5.52(d,J=6.4Hz,1H),4.76-4.71(m,2H),4.52(dd,J=11.6,5.2Hz,1H),4.07(t,J=6. 4Hz, 1H), 3.96 (q, J = 6.4, 2.4Hz, 1H), 3.53-3.47 (m, 1H), 3.41-3.36 (m, 1H), 3.08 (s, 3H).

[0685] Example 24

[0686] 5-Chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0687]

[0688] Add 4-(2-trimethylsilylethynyl)thiazolyl-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) to a solution of 5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (40 mg, 0.094 mmol) in DMF (2 mL) and stir the mixture overnight at room temperature. 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, UV 254] to give the title compound (8.0 mg, 16%). ESI-MS m / z, for [C 22 H 26 ClN7O4S2][M+H] + Calculated value: 552.1; Measured value: 551.8. 1¹H NMR (400MHz, 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, 1H), 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).

[0689] Example 25

[0690] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside

[0691]

[0692] TFA (248 mg, 2.16 mmol) and H2O (0.5 mL) were added to a solution of 5-chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-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) and the mixture was stirred at room temperature for 12 h. Et3N (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, UV 254] to give the title compound (33 mg, 73%). ESI-MS m / z, for [C 24 H 20 ClF2N7O5S2][M+H] + Calculated value: 624.1; Measured value: 624.1. 1H NMR (400MHz, methanol-d4) δ8.51(d,J=2.0Hz,1H),8.34(d,J=2.0Hz,1H),8.04(s,1H),6.87(s,1H),6.62-6.54(m,2H),6.29(d,J=5.2Hz,1H),5.01 (dd,J=11.2,2.8Hz,1H),4.70(dd,J=11.2,5.2Hz,1H),4.56(d,J=11.6Hz,1H),4.33-4.26(m,2H),4.10(d,J=2.4Hz,1H),3.63-3.55(m,2H).

[0693] Example 26

[0694] 5-Chloro-2-(pyridin-2-yl)pyridin-3-yl3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0695]

[0696] A solution of 5-chloro-2-(pyridin-2-yl)pyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-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 room temperature for 1 h. The mixture was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the title compound (14.5 mg, 48%). ESI-MS m / z, for [C 22 H 22 ClN7O4S2][M+H] + Calculated value: 548.1; Measured value: 548.0. 1H NMR (400MHz, methanol-d4) δ8.58(d,J=4.4Hz,1H),8.42(d,J=2.4Hz,1H),8.36(d,J=2.4Hz,1 H),8.09(s,1H),7.89(td,J=7.6,1.6Hz,1H),7.75(d,J=7.6Hz,1H),7.41(ddd,J=7.6, 5.2,0.8Hz,1H),6.83(s,1H),6.09(d,J=5.2Hz,1H),4.78(m,1H),4.41(dd,J=11.2,5. 2Hz, 1H), 4.18 (t, J = 6.0Hz, 1H), 4.01 (d, J = 2.4Hz, 1H), 3.65-3.50 (m, 2H), 3.08 (s, 3H).

[0697] Example 27

[0698] 5-Chloro-2-(oxazol-2-yl)pyridin-3-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0699]

[0700] TFA (528 mg, 4.63 mmol) and H2O (0.5 mL) were added to a solution of 5-chloro-2-(oxazol-2-yl)pyridin-3-yl 4,6-O-benzyl-3-[4-(N-tert-butoxycarbonyl-2-aminothiazo-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), and the mixture was stirred at room temperature for 12 h. Et3N (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, UV 254] to give the title compound (16 mg, 26%). ESI-MS m / z, for [C 20 H 20 ClN7O5S2][M+H] + Calculated value: 538.1; Measured value: 538.0. 1H NMR (400MHz, methanol-d4) δ8.43(d,J=2.0Hz,1H),8.38(d,J=2.0Hz,1H),8.15(s,1H),8.03(s,1H),7.36(s,1H),6.86(s,1H),6.39(d,J=5.6Hz, 1H), 4.98 (dd, J=11.2, 2.8Hz, 1H), 4.53 (dd, J=11.2, 5.2Hz, 1H), 4.25-4.22 (m, 1H), 4.07 (d, J=2.4Hz, 1H), 3.60-3.53 (m, 2H), 3.26 (s, 3H).

[0701] Example 28

[0702] 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

[0703]

[0704] A solution of 3,4-dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-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 room temperature for 1 h. The mixture was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the title compound (37.5 mg, 49%). ESI-MS m / z, for [C 18 H 19 Cl2N5O4S2][M+H] + Calculated value: 504.0; Measured value: 504.0. 1H NMR (400MHz, methanol-d4) δ8.25(s,1H),7.81(d,J=2.0Hz,1H),7.54(dd,J=8.4,2.0Hz,1H),7.47(d,J=8.4Hz,1H),6.96(s,1H),6.16(d,J=5.2Hz,1 H), 4.98 (dd, J=11.2, 1.6Hz, 1H), 4.55 (dd, J=11.2, 5.2Hz, 1H), 4.45 (t, J=6.4Hz, 1H), 4.18 (s, 1H), 3.69 (qd, J=11.6, 6.4Hz, 2H), 3.37 (s, 3H).

[0705] Example 29

[0706] 5-Chloro-2-(thiazo-2-yl)pyridin-3-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0707]

[0708] TFA (192 mg, 1.68 mmol) and H2O (0.5 mL) were added to a solution of 5-chloro-2-(thiazol-2-yl)pyridin-3-yl 4,6-O-benzyl-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) and the mixture was stirred at room temperature for 12 h. Et3N (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, UV 254] to give the title compound (2.7 mg, 14%). ESI-MS m / z, for [C 20 H 20 ClN7O4S3][M+H] + Calculated value: 554.0; Measured value: 554.0. 1H NMR (400MHz, methanol-d4) δ8.44(dd,J=6.8,2.0Hz,2H),8.27(s,1H),8.02(d,J=3.2Hz,1H),7.71(d,J=3.2Hz,1H),6.98(s,1H),6.52(d,J=5.6Hz ,1H),5.15(dd,J=11.2,2.8Hz,1H),4.66(dd,J=11.2,5.2Hz,1H),4.38-4.35(m,1H),4.19(d,J=2.8Hz,1H),3.74-3.64(m,2H),3.38(s,3H).

[0709] Example 30

[0710] 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

[0711]

[0712] A solution of 3-chloro-4-(trifluoromethyl)phenyl 4,6-O-benzyl-3-[4-(N-tert-butoxycarbonyl-2-aminothiazolyl-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 room temperature for 6 h. The mixture was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the title compound (102 mg, 54%). ESI-MS m / z, for [C 19 H 19 ClF3N5O4S2][M+H] + Calculated value: 538.1; Measured value: 538.0. 1 H NMR (400MHz, methanol-d4) δ8.27(s,1H),7.88(s,1H),7.72(d,J=7.6Hz,2H),6.98(s,1H),6.41(d,J=5.6Hz,1H),5.02(dd,J=1 1.6, 2.8Hz, 1H), 4.62 (dd, J = 11.2, 5.2Hz, 1H), 4.43-4.40 (m, 1H), 4.20 (d, J = 2.0Hz, 1H), 3.76-3.66 (m, 2H), 3.40 (s, 3H).

[0713] Example 31

[0714] 3-Chlorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0715]

[0716] TFA (0.409 mL, 5.50 mmol) was added to a solution of 3-chlorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (70 mg, 0.13 mmol) in DCM (10 mL), and the mixture was stirred at room temperature for 2 h. Et3N (1 mL) was added at 0 °C, and the mixture was concentrated. The residue was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to provide the title compound (16.0 mg, 27%). ESI-MS m / z, for [C 18 H 20 ClN5O4S2][M+H] + Calculated value: 470.1; Measured value: 470.0. 1 ¹H NMR (400MHz, 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).

[0717] Example 32

[0718] 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

[0719]

[0720] 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), Et3N (2.49 mL, 17.9 mmol), and water (829 mg, 46 mmol) was stirred overnight at room temperature. The mixture was concentrated and purified by column chromatography (MeCN / H2O = 1 / 20–1 / 7, C-18 column, 20 mL / min, UV 254) to provide the title compound (36.0 mg, 60%). ESI-MS m / z, for [C 17 H 16 Cl2FN5O4S2][M+H] + Calculated value: 508.0; Measured value: 508.0. 1 ¹H NMR (400MHz, 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).

[0721] Example 33

[0722] 3-Bromo-2-(trifluoromethyl)pyridin-5-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0723]

[0724] A solution of 3-bromo-2-(trifluoromethyl)pyridin-5-yl 2,4,6-tri-O-acetyl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (13.0 mg, 0.018 mmol) in MeOH / Et3N / H2O (9 mL, 5:3:1) was stirred overnight at room temperature. 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, UV 254] to give the title compound (8.70 mg, 71%). ESI-MS m / z, for [C 18 H 18BrF3N6O4S2][M+H] + Calculated value: 583.0; Measured value: 583.0. 1 H NMR (400MHz, methanol-d4) δ8.74(d,J=1.6Hz,1H),8.50(d,J=1.6Hz,1H),8.19(s,1H),6.11(d,J=5.6Hz,1H),5.02(dd,J= 11.2, 2.8Hz, 1H), 4.95-4.91 (m, 1H), 4.39 (t, J = 6.0Hz, 1H), 4.18 (d, J = 2.0Hz, 1H), 3.75-3.57 (m, 2H), 2.52 (s, 3H).

[0725] Example 34

[0726] 5-Bromo-2-cyanopyridin-3-yl-3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0727]

[0728] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-deoxy-3-[4-(4-methylthiazo-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), Et3N (2.0 mL), and water (1.0 mL) was stirred at room temperature for 4 h. 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, UV 254) to give the title compound (34.0 mg, 76%). ESI-MS m / z, for [C 19 H 19 BrN6O4S2][M+H] + Calculated value: 539.0; Measured value: 539.1. 1H NMR (400MHz, methanol-d4) δ8.73(d,J=2.0Hz,1H),8.65(d,J=2.0Hz,1H),8.61(s,1H),7.20(d,J=0.8Hz,1H),6.53(d,J=5.2Hz,1H),5.15(dd ,J=11.2,2.8Hz,1H),4.74-4.70(m,1H),4.43(t,J=6.0Hz,1H),4.23(d,J=2.4Hz,1H),3.70(d,J=6.0Hz,2H),3.49(s,3H),2.49(s,3H).

[0729] Example 35

[0730] 2-Cyano-5-methylpyridin-3-yl-3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0731]

[0732] A solution of 2-cyano-5-methylpyridin-3-yl 4,6-O-benzyl-3-deoxy-3-[4-(4-methylthiazo-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 room temperature for 6 h. Et3N 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 provide the title compound (58.0 mg, 75%). ESI-MS m / z, for [C 20 H 22 N6O4S2][M+H] + Calculated value: 475.1; Measured value: 475.2. 1H NMR (400MHz, methanol-d4) δ8.58 (s, 1H), 8.46 (dd, J=2.0, 0.8Hz, 1H), 8.20 (dd, J= 2.0,0.8Hz,1H),7.17(d,J=0.8Hz,1H),6.37(d,J=5.2Hz,1H),5.12(dd,J=11 .2,2.8Hz,1H),4.67(dd,J=11.2,5.2Hz,1H),4.47(t,J=6.0Hz,1H),4.21(d, J=2.4Hz,1H),3.67(d,J=6.0Hz,2H),3.47(s,3H),2.47(s,3H),2.44(s,3H).

[0733] Example 36

[0734] 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

[0735]

[0736] A solution of 2-cyano-5-methylpyridin-3-yl 4,6-O-benzyl-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 room temperature for 6 h. Et3N 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, UV 254] to provide the title compound (95.0 mg, 51%). ESI-MS m / z, for [C 19 H 19 ClN6O4S2][M+H] + Calculated value: 495.1; Measured value: 495.2. 1H NMR (400MHz, methanol-d4) δ8.64(s,1H),8.45(d,J=1.6Hz,1H),8.20(dd,J=1.6,0.8Hz,1H),7.46(s,1H),6.36(d,J=5.2Hz,1H),5.12(dd,J=11. 2,3.2Hz,1H),4.69(dd,J=11.2,2.8Hz,1H),4.46(t,J=6.0Hz,1H),4.21(d,J=2.4Hz,1H),3.67(d,J=6.0Hz,2H),3.47(s,3H),2.44(s,3H).

[0737] Example 37

[0738] 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

[0739]

[0740] TFA (0.406 mL, 5.47 mmol) was added to a solution of 5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 4,6-O-benzyl-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), and the mixture was stirred overnight at room temperature. Et3N (1 mL) was added at 0 °C to neutralize the TFA, and the mixture was concentrated. The residue was dissolved in DMF (3 mL), and KF (6.35 mg, 0.11 mmol) was added, and the mixture was stirred at room temperature 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 provide the title compound (13.5 mg, 52%). ESI-MS m / z, for [C 19 H 18 ClN5O4S2][M+H] + Calculated value: 480.0; Measured value: 480.2. 1H NMR (400MHz, methanol-d4) δ8.70(d,J=2.0Hz,1H),8.63(s,1H),8.54(d,J=1.6Hz,1H),8.20(t,J=2.0Hz,1H),7.46(s,1H),6.24(d,J=5.2Hz,1H) ,5.08(dd,J=11.2,2.8Hz,1H),4.63(dd,J=11.2,5.2Hz,1H),4.47(t,J=6.0Hz,1H),4.20(d,J=2.4Hz,1H),3.76-3.57(m,2H),3.41(s,3H).

[0741] Example 38

[0742] 5-Chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptyl}-pyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0743]

[0744] A solution of 5-chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptyl}-pyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-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 room temperature for 1 h. Et3N 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, UV 254] to provide the title compound (39.6 mg, 38%). ESI-MS m / z, for [C 22 H 26 ClN7O5S2][M+H] + Calculated value: 568.1; Measured value: 568.0. 1H NMR (400MHz, DMSO-d6) δ8.18(s,1H),8.08(d,J=2.4Hz,1H),7.85(d,J=2.4Hz,1H),7.10(s,2H),6.92( s,1H),6.04(d,J=5.2Hz,1H),5.52(d,J=6.8Hz,1H),4.87(dd,J=11.6,2.0Hz,1H),4.77(t,J=5.2Hz,1H ),4.74-4.62(m,4H),4.53(dd,J=11.2,5.2Hz,1H),4.36(d,J=9.2Hz,2H),4.29(d,J=9.2Hz,2H),4.25 (t, J=6.0Hz, 1H), 4.03 (d, J=3.6Hz, 1H), 3.57-3.49 (m, 1H), 3.40 (dd, J=11.6, 6.0Hz, 1H), 3.29 (s, 3H).

[0745] Example 39

[0746] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0747]

[0748] 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), Et3N (3.0 mL), and water (1.0 mL) was stirred overnight at room temperature. 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 (8.8 mg, 41%). ESI-MS m / z, for [C 19 H 19 ClN6O4S2][M+H] + Calculated value: 495.1; Measured value: 495.0. 1¹H NMR (400MHz, 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).

[0749] Example 40

[0750] 5-Cyanopyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0751]

[0752] A solution of 5-cyanopyridin-3-yl 4,6-O-benzyl-3-{4-[2-(di-tert-butoxycarbonylamino)thiazolyl-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 room temperature. The mixture was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the title compound (40.2 mg, 59%). ESI-MS m / z, for [C 18 H 19 N7O4S2][M+H + Calculated value: 462.1; Measured value: 462.1. 1 H NMR (400MHz, methanol-d4) δ8.95(d,J=2.4Hz,1H),8.79(d,J=2.0Hz,1H),8.49(t,J=2.0Hz,1H),8.24(s,1H),6.95(s,1H),6.33(d,J=5.6Hz,1H),5 .03(dd,J=11.2,2.8Hz,1H), 4.59(dd,J=11.2,5.6Hz,1H), 4.42(t,J=6.0Hz,1H), 4.17(d,J=2.4Hz,1H), 3.68(d,J=6.0Hz,2H), 3.39(s,3H).

[0753] Example 41

[0754] 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

[0755]

[0756] HBr (1 mL) was added to a suspension of 4,6-di-O-acetyl-3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-D-galactosene (400 mg, 1.05 mmol) in THF (20 mL), and the mixture was stirred at room temperature for 22 h. Water (10 mL) was added, followed by Na₂CO₃ (446 mg, 4.21 mmol), and the mixture was stirred at room temperature for 30 min. The mixture was concentrated and stirred at room temperature for 24 h in pyridine (10 mL) and acetic anhydride (10 mL). 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-benzylthioalkyl-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), and the resulting mixture was brought to room temperature within 15 min and then stirred at room temperature for 2 h. The mixture was cooled to 0 °C and quenched by adding water. The phases were separated, and the organic phase was washed with water, dried, and concentrated. The residue and crude acetyl-3-[4-(2-acetoxythiazo-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 ether (0.11 mL, 0.91 mmol) was added, and the mixture was stirred at room temperature for 16 h. The mixture was diluted with DCM and washed with a saturated aqueous solution of 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 H2O (0.5 mL) at room temperature for 28 h. The mixture was evaporated and purified by preparative HPLC (C 18H2O / MeCN / 0.1% TFA) to provide the title compound (6.6 mg, 1.3%). ESI-MS m / z, for [C 17 H 15 Cl2FN4O4S2][M+H] + Calculated value: 493.0; Measured value: 492.7 1 H NMR (500MHz, methanol-d4) δ8.31(s,1H),7.73(d,J=6.2Hz,2H),6.70(s,1H),5.93(d,J=5.5Hz,1H),5.17(ddd,J=13.6,3.9,2.5Hz,1H) ,4.50(t,J=6.1Hz,1H), 4.17(d,J=2.2Hz,1H), 3.76(d,J=6.0Hz,2H), 3.10(td,J=13.5,5.8Hz,1H), 2.33(dd,J=13.4,4.3Hz,1H).

[0757] Example 42

[0758] 3-Chloro-4-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-2,3-dideoxy-1-thio-α-D-galactopyranoside

[0759]

[0760] 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-galactosene (100 mg, 0.26 mmol) in THF (7.5 mL), and the mixture was stirred at room temperature for 3 h. Water (2.5 mL) was added, followed by Na₂CO₃ (56 mg, 0.53 mmol), and the mixture was stirred at room temperature for 40 min. The mixture was concentrated and stirred at room temperature for 2 h in pyridine (3 mL) and acetic anhydride (3 mL). The mixture was concentrated and partitioned between EtOAc and water. The organic phase was dried, evaporated, and purified by chromatography (SiO₂, PE / EtOAc). The obtained material was dissolved in DCM (3 mL) with 2-chloro-4-thioalkylbenzyl nitrile (53 mg, 0.31 mmol). Add boron trifluoride diethyl ether (0.10 mL, 0.83 mmol) and stir the mixture at room temperature for 18 h. Dilute the mixture with DCM and wash with saturated NaHCO3 aqueous solution. Dry the organic phase, evaporate, and stir the residue in methylamine (40% in MeOH, 2 mL) at 50 °C for 50 h. Evaporate the mixture and purify by preparative HPLC (C10-C20).18 H2O / MeCN / 0.1% TFA) to provide the title compound (21 mg, 17%). ESI-MS m / z, for [C 18 H 17 ClN6O3S2][M+H] + Calculated value: 465.0; Measured value: 464.8 1 H NMR (400MHz, methanol-d4) δ8.42(s,1H),7.85(d,J=1.5Hz,1H),7.71(d,J=8.2Hz,1H),7.64(dd,J=8.2,1.6Hz,1H),7.09(s,1H),6.19(d,J=5.6Hz,1H), 5.20(dt,J=13.6,3.4Hz,1H),4.39(t,J=6.1Hz,1H),4.18(s,1H),3.78- 3.70(m,2H), 3.16(td,J=13.5,5.6Hz,1H), 2.35(dd,J=13.6,4.1Hz,1H).

[0761] Example 43

[0762] 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

[0763]

[0764] 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-galactosene (100 mg, 0.25 mmol) in THF (5 mL), and the mixture was stirred at room temperature for 3 h. Water (2.5 mL) was added, followed by Na₂CO₃ (53 mg, 0.50 mmol), and the mixture was stirred at room temperature 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 obtained material was dissolved in DCM (5 mL) with 4-chloro-2-thioalkylbenzyl nitrile (39 mg, 0.23 mmol). Trifluoromethanesulfonic acid (41 μL, 0.46 mmol) was added, and the mixture was stirred at room temperature for 1 h. The mixture was diluted with DCM and washed with a saturated aqueous NaHCO3 solution. The organic phase was dried, evaporated, and purified by chromatography (SiO2, PE / EtOAc). The obtained material was stirred in MeOH (4 mL) and NaOMe (0.5 mL, 1 M) at room temperature for 20 min. The mixture was concentrated and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA) to provide the title compound (11 mg, 9%). ESI-MS m / z, for [C 18 H 15 Cl2N5O3S2][M+H] + Calculated value: 484.0; Measured value: 484.0 1 H NMR (400MHz, methanol-d4) δ8.58(s,1H),8.02(d,J=2.0Hz,1H),7.74(d,J=8.4Hz,1H),7.50-7.44(m,2H),6.16(d,J=5.5Hz,1H),5.26(d, J=13.0Hz,1H),4.46(t,J=6.0Hz,1H),4.23(s,1H),3.79-3.68(m,2H),3.22(td,J=13.5,5.8Hz,1H),2.45(dd,J=13.7,4.5Hz,1H).

[0765] Example 44

[0766] 3-Cyano-2-(trifluoromethyl)pyridin-5-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0767]

[0768] 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 N-[4-(2-trimethylsilylethynyl)thiazo-2-yl]tert-butyl carbamate (38 mg, 0.13 mmol) in MeCN (1.0 mL), TBAF (106 μL, 0.11 mmol in THF, 1 M) was added, and the mixture was stirred at room temperature for 5 h. The mixture was diluted with EtOAc (20 mL) and washed with water (3 x 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 room temperature for 16 h. The mixture was evaporated, and the residue was stirred in MeOH (2 mL) and NaOMe (0.11 mL, 1 M) at room temperature for 20 min. Acetic acid (20 μL) was added, and the mixture was concentrated and purified by preparative HPLC (C10). 18 H2O / MeCN / 0.1% TFA) to provide the title compound as a TFA salt (23 mg, 34%). ESI-MS m / z, for [C 19 H 18 F3N7O4S2][M+H] + Calculated value: 530.1; Measured value: 529.9 1 H NMR (400MHz, methanol-d4) δ9.03(d,J=2.0Hz,1H),8.68(d,J=2.0Hz,1H),8.26(s,1H),6.97(s,1H),6.57(d,J=5.3Hz,1H),5.06(dd,J=1 1.2, 2.7Hz, 1H), 4.64 (dd, J = 11.3, 5.3Hz, 1H), 4.35 (dd, J = 7.1, 4.7Hz, 1H), 4.17 (d, J = 2.4Hz, 1H), 3.78-3.63 (m, 2H), 3.40 (s, 3H).

[0769] Example 45

[0770] 5-Chloro-2-(N-azacyclobutylcarbamoyl)-3-pyridyl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0771]

[0772] DIPEA (61 μL, 0.36 mmol) was added to a solution of 5-chloro-2-(N-azacyclobutylcarbamoyl)-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), and the mixture was stirred at 50 °C for 2 h. The mixture was then purified by preparative HPLC (C10-C2 ... 18 H2O / MeCN / 0.1% TFA) to provide the title compound (48 mg, 71%). ESI-MS m / z, for [C 21 H 22 Cl2N6O5S2][M+H] + Calculated value: 573.0; Measured value: 572.8. 1 H NMR (400MHz, methanol-d4) δ8.63(s,1H),8.48(d,J=2.1Hz,1H),8.38(d,J=2.1Hz,1H),7.47(d,J=2.7Hz,1H),6.36(d,J=5.4Hz,1H),5.11(dd,J=11. 3, 2.9Hz, 1H), 4.66 (dd, J = 11.4, 5.4Hz, 1H), 4.44 (t, J = 6.0Hz, 1H), 4.27-4.16 (m, 5H), 3.74-3.64 (m, 2H), 3.41 (s, 3H), 2.39 (p, J = 7.8Hz, 2H).

[0773] Example 46

[0774] 5-Chloro-2-(pyridin-2-yl)pyridin-3-yl3-deoxy-3-[4-(4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0775]

[0776] DIPEA (92 μL, 0.54 mmol) was added to a solution of 5-chloro-2-(pyridin-2-yl)pyridin-3-yl-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-methylthiazolyl-2-yl)ethynyl]silane (44 mg, 0.22 mmol) in MeCN (2.0 mL), and the mixture was stirred at 50 °C for 2 h. The mixture was concentrated and partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic phase was dried, evaporated, and purified by preparative HPLC (C6000-C6000). 18 H2O / MeCN / 0.1% TFA) to provide the title compound (41 mg, 42%). ESI-MS m / z, for [C 23 H 23 ClN6O4S2][M+H] + Calculated value: 547.1; Measured value: 547.1. 1 H NMR (500MHz, methanol-d4) δ8.80(d,J=5.0Hz,1H),8.62(d,J=2.1Hz,1H),8.55-8.52(m,2H),8.2 9(td,J=7.8,1.6Hz,1H),8.22(d,J=7.9Hz,1H),7.79-7.74(m,1H),7.18(d,J=1.0Hz,1H),6 .25(d,J=5.3Hz,1H),4.98(dd,J=11.4,2.9Hz,1H),4.58(dd,J=11.4,5.3Hz,1H),4.24(t,J =6.1Hz, 1H), 4.13 (d, J = 2.3Hz, 1H), 3.70-3.64 (m, 2H), 3.23 (s, 3H), 2.47 (d, J = 0.9Hz, 3H).

[0777] Example 47

[0778] 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

[0779]

[0780] 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 followed by the addition of ethynyl(trimethyl)silane (11.6 μL, 0.084 mmol), then DIPEA (14.6 μL, 0.084 mmol), and the mixture was stirred at 50 °C for 20 h. The mixture was cooled to room temperature and TBAF (0.15 mL, 1 M, 0.15 mmol in THF) was added. After stirring at room temperature for 30 min, the mixture was partitioned between EtOAc and water. The organic phase was dried, evaporated, and purified by preparative HPLC (C1). 18 H2O / MeCN / 0.1% TFA) to provide the title compound (14 mg, 52%). ESI-MS m / z, for [C 19 H 19 N5O4S2][M+H] + Calculated value: 446.1; Measured value: 446.1. 1 H NMR (400MHz, methanol-d4) δ8.65(d,J=1.9Hz,1H),8.51(s,1H),8.48(s,1H),8.18(t,J =2.0Hz,1H),7.79(d,J=3.0Hz,1H),7.54(d,J=3.1Hz,1H),6.19(d,J=5.3Hz,1H) ,4.99(dd,J=11.3,2.8Hz,1H),4.54(dd,J=11.3,5.3Hz,1H),4.36(t,J=6.0Hz,1 H), 4.11 (d, J = 2.2Hz, 1H), 3.80 (s, 1H), 3.64-3.54 (m, 2H), 3.31 (d, J = 2.0Hz, 3H).

[0781] Example 48

[0782] 5-Chloropyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0783]

[0784] 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), Et3N (0.11 mL, 0.80 mmol) and TBAF (0.02 mL, 1 M in THF, 0.020 mmol) were added, and the mixture was stirred at 50 °C for 90 min. The mixture was filtered through a diatomaceous earth mat and concentrated. The residue was stirred at room temperature for 16 h in MeOH (1 mL), Et3N (0.45 mL), and water (0.15 mL). The mixture was filtered, concentrated, and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA) to provide the title compound (61 mg, 64%). ESI-MS m / z, for [C 16 H 15 Cl2N5O4S2][M+H] + Calculated value: 476.0; Measured value: 476.0. 1 H NMR (500MHz, methanol-d4) δ8.68(s,1H),8.62(s,1H),8.51(s,1H),8.24(t,J=2.0Hz,1H),7.48(s,1H),5.96(d,J=5.4Hz,1H),5. 09(dd,J=11.4,2.9Hz,1H), 4.96(dd,J=11.4,5.4Hz,1H), 4.50(t,J=6.1Hz,1H), 4.24(d,J=2.0Hz,1H), 3.77-3.68(m,2H).

[0785] Example 49

[0786] 5-Bromopyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0787]

[0788] 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 K₂CO₃ (2.05 g, 14.8 mmol) in MeOH / THF (35 mL, 1:1). The mixture was stirred at room temperature for 16 h, followed by stirring 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 produce the title compound (589 mg, 76%). ESI-MS m / z, for [C 16 H 15 BrClN5O4S2][M+H] + Calculated value: 519.9; Measured value: 519.9. 1 H NMR (400MHz, methanol-d4) δ8.69(d,J=1.8Hz,1H),8.60(s,1H),8.58(d,J=2.1Hz,1H),8.36(t,J=2.0Hz,1H),7.47(s,1H),5.93(d,J=5.4H z, 1H), 5.07 (dd, J = 11.4, 2.9Hz, 1H), 4.93 (dd, J = 11.4, 5.4Hz, 1H), 4.48 (t, J = 6.1Hz, 1H), 4.21 (d, J = 2.0Hz, 1H), 3.76-3.66 (m, 2H).

[0789] Example 50

[0790] 5-Chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0791]

[0792] 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), Et3N (0.14 mL, 1.04 mmol) and TBAF (26 μL, 1 M in THF, 0.026 mmol) were added and the mixture was stirred at 50 °C for 90 min. The mixture was filtered, concentrated, and the residue was stirred at 50 °C for 16 h in MeOH (2 mL), Et3N (0.3 mL), and water (0.1 mL). The mixture was filtered, concentrated, and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA). The obtained material was filtered through an SCX column to provide the title compound (93 mg, 72%). ESI-MS m / z, for [C 16 H 15 Cl2N5O4S2][M+H] + Calculated value: 500.0; Measured value: 500.0. 1 H NMR (400MHz, methanol-d4) δ8.61(s,1H),7.98(d,J=1.9Hz,1H),7.74(d,J=8.3Hz,1H),7.51-7.43(m,2H),6.13(d,J=5.3Hz,1H),5.11(dd,J=11.3,2 .8Hz,1H),4.98(dd,J=11.4,5.4Hz,1H),4.42(t,J=6.2Hz,1H),4.28-4.21(m,1H),3.70(dd,J=11.4,5.6Hz,1H),3.64(dd,J=11.4,6.6Hz,1H).

[0793] Example 51

[0794] 3-Chloro-5-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0795]

[0796] 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), Et3N (92 μL, 0.66 mmol) and TBAF (17 μL, 1 M in THF, 0.017 mmol) were added and the mixture was stirred at 50 °C for 1 h. The mixture was filtered, concentrated, and the residue was stirred at 50 °C for 16 h in MeOH (2 mL), Et3N (0.3 mL), and water (0.1 mL). The mixture was filtered, concentrated, and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA). The obtained material was filtered through an SCX column to provide the title compound (35 mg, 42%). ESI-MS m / z, for [C 16 H 15 Cl2N5O4S2][M+H] + Calculated value: 500.0; Measured value: 500.0. 1 HNMR (400MHz, methanol-d4) δ8.60(s,1H),7.95(s,1H),7.93(s,1H),7.71(s,1H),7.46(s,1H),5.98(d,J=5.2Hz,1H),5.05 (dd,J=11.5,2.7Hz,1H),4.93(dd,J=11.5,5.4Hz,1H),4.44(t,J=6.2Hz,1H),4.23-4.17(m,1H),3.77-3.65(m,2H).

[0797] Example 52

[0798] 3-Chloro-4-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0799]

[0800] 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), Et3N (128 μL, 0.92 mmol) and TBAF (23 μL, 1 M in THF, 0.023 mmol) were added and the mixture was stirred at 50 °C for 90 min. The mixture was filtered, concentrated, and the residue was stirred at 50 °C for 20 h in MeOH (2 mL), Et3N (0.3 mL), and water (0.1 mL). The mixture was filtered, concentrated, and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA). The obtained material was filtered through an SCX column to provide the title compound (81 mg, 70%). ESI-MS m / z, for [C 16 H 15 Cl2N5O4S2][M+H] + Calculated value: 500.0; Measured value: 500.0. 1 H NMR (400MHz, methanol-d4) δ8.60(s,1H),7.86(d,J=1.4Hz,1H),7.71(d,J=8.3Hz,1H),7.66(dd,J=8.2,1.5Hz,1H),7.46(s,1H),6.11(d,J= 5.3Hz, 1H), 5.06 (dd, J = 11.4, 2.8Hz, 1H), 4.96 (dd, J = 11.3, 5.5Hz, 1H), 4.38 (t, J = 6.1Hz, 1H), 4.23-4.17 (m, 1H), 3.77-3.63 (m, 2H).

[0801] Example 53

[0802] 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

[0803]

[0804] Et3N (112 μL, 0.80 mmol) and TBAF (20 μL, 1 M in THF, 0.020 mmol) were added to a solution of 5-chloropyridin-3-yl-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), and the mixture was stirred at 50 °C for 90 min. The mixture was filtered, concentrated, and purified by preparative HPLC (C10). 18 H2O / MeCN / 0.1% TFA) to provide the title compound (13 mg, 13%). ESI-MS m / z, for [C 17 H 17 Cl2N5O4S2][M+H] + Calculated value: 490.0; Measured value: 490.0. 1 H NMR (500MHz, methanol-d4) δ8.68(s,1H),8.66(s,1H),8.50(s,1H),8.24(t,J=2.0Hz,1H),7.49(s,1H),6.30(d,J=5.3Hz,1H),5.11(dd ,J=11.4,2.9Hz,1H),4.67(dd,J=11.3,5.3Hz,1H),4.49(t,J=6.1Hz,1H),4.22(d,J=2.2Hz,1H),3.78-3.66(m,2H),3.44(s,3H).

[0805] Example 54

[0806] 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

[0807]

[0808] Add benzaldehyde dimethyl acetal (0.30 mL, 1.98 mmol) 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), then add p-toluenesulfonic acid monohydrate (94 mg, 0.50 mmol) and stir the mixture at room temperature for 20 h. Add Et3N (0.14 mL, 0.99 mmol) and concentrate the mixture. Partition the residue between EtOAc and a saturated aqueous solution of NaHCO3. Dry the organic phase, evaporate, and dissolve the residue in DMF (5 mL) along with NaH (60% in oil, 60 mg, 1.56 mmol). Add iodomethane (78 μL, 1.17 mmol) and stir the mixture at room temperature for 1 h. The mixture was diluted with EtOAc, washed twice with water, and the organic phase was dried and evaporated. The residue was stirred in TFA / water (5 mL, 4:1) at room temperature for 30 min. The mixture was concentrated to half its volume and partitioned between EtOAc and NaOH aqueous solution (1 M). The organic phase was dried, evaporated, and purified by chromatography (SiO2, PE / EtOAc). Further purification was performed by preparative HPLC (C). 18 H2O / MeCN / 0.1% TFA) produced the title compound (191 mg, 46%). ESI-MS m / z, for [C 17 H 17 BrClN5O4S2][M+H] + Calculated value: 534.0; Measured value: 534.0. 1 H NMR (500MHz, methanol-d4) δ8.74(s,1H),8.65(s,1H),8.62(s,1H),8.41(t,J=1.9Hz,1H),7.49(s,1H),6.31(d,J=5.3Hz,1H),5.11(dd ,J=11.3,2.9Hz,1H),4.67(dd,J=11.3,5.3Hz,1H),4.48(t,J=6.1Hz,1H),4.23(d,J=2.3Hz,1H),3.76-3.68(m,2H),3.44(s,3H).

[0809] Example 55

[0810] 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

[0811]

[0812] DIPEA (77 μL, 0.45 mmol) was added 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), 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 (SiO2, PE / EtOAc). The obtained material was stirred at room temperature for 3 h in MeOH (2.25 mL), Et3N (0.75 mL), and water (0.25 mL). The mixture was concentrated and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA) to provide the title compound (60 mg, 67%). ESI-MS m / z, for [C 18 H 15 BrCl2N6O4S2][M+H] + Calculated value: 592.9; Measured value: 592.9. 1 H NMR (400MHz, methanol-d4) δ8.71(d,J=2.0Hz,1H),8.67(s,1H),8.62(d,J=2.0Hz,1H),6.50(d,J=5.3Hz,1H),5.13(dd,J=11.3,2 .9Hz, 1H), 4.72 (dd, J = 11.3, 5.3Hz, 1H), 4.41 (t, J = 6.0Hz, 1H), 4.20 (d, J = 2.6Hz, 1H), 3.68 (d, J = 6.0Hz, 2H), 3.46 (s, 3H).

[0813] Example 56

[0814] 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

[0815]

[0816] Et3N (101 μL, 0.72 mmol) and TBAF (18 μL, 0.018 mmol in 1 M THF) were added 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), and the mixture was stirred at 50 °C for 5 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C10-C2 ... 18 H2O / MeCN / 0.1% TFA). The obtained material was further purified by chromatography (SiO2, PE / EtOAc) to provide the title compound (30 mg, 32%). ESI-MS m / z, for [C 19 H 18 BrN5O4S2][M+H] + Calculated value: 524.0; Measured value: 524.0. 1 H NMR (500MHz, methanol-d4) δ8.64(s,1H),8.18(d,J=1.5Hz,1H),7.92(d,J=3.3Hz,1H), 7.73-7.68(m,2H),7.67(d,J=3.3Hz,1H),6.42(d,J=5.4Hz,1H),5.14(dd,J=11.3 ,2.9Hz,1H),4.71(dd,J=11.3,5.3Hz,1H),4.47(t,J=6.1Hz,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).

[0817] Example 57

[0818] 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

[0819]

[0820] Et3N (101 μL, 0.72 mmol) and TBAF (18 μL, 0.018 mmol in 1 M THF) were added 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), and the mixture was stirred at 50 °C for 4 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C10-C2 ... 18 H2O / MeCN / 0.1% TFA) to provide the title compound (71 mg, 70%). ESI-MS m / z, for [C 19 H 17 BrClN5O4S2][M+H] + Calculated value: 558.0; Measured value: 558.0. 1 H NMR (500MHz, methanol-d4) δ8.66(s,1H),8.17(s,1H),7.73-7.66(m,2H),7.49(s,1H),6.42(d,J=5.3Hz,1H),5.13(dd,J=11.3,2.9Hz,1H),4.72(d d,J=11.3,5.3Hz,1H),4.47(t,J=6.1Hz,1H),4.25(d,J=2.7Hz,1H),3.73(dd,J=11.5,5.5Hz,1H),3.67(dd,J=11.4,6.7Hz,1H),3.49(s,3H).

[0821] Example 58

[0822] 5-Bromo-2-cyanophenyl-3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0823]

[0824] Add Et3N (101 μL, 0.72 mmol) and TBAF (18 μL, 0.018 mmol in 1 M THF) 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) and stir the mixture at 50 °C for 4 h. Add more 4-(2-trimethylsilylethynyl)thiazol-2-ol (54 mg, 0.27 mmol) and stir the mixture at 50 °C for another 2 h. Filter the mixture, concentrate it, and purify it by preparative HPLC (C60000). 18 H2O / MeCN / 0.1% TFA) to provide the title compound (45 mg, 46%). ESI-MS m / z, for [C 19 H 18 BrN5O5S2][M+H] + Calculated value: 540.0; Measured value: 540.0. 1 H NMR (500MHz, methanol-d4) δ8.39(s,1H),8.17(d,J=1.0Hz,1H),7.73-7.66(m,2H),6.73(s,1H),6.41(d,J=5.3Hz,1H),5.08(dd,J=11.3,2.9Hz,1H),4. 63(dd,J=11.3,5.3Hz,1H), 4.45(t,J=6.0Hz,1H), 4.23(d,J=2.3Hz,1H), 3.72(dd,J=11.4,5.5Hz,1H), 3.66(dd,J=11.4,6.7Hz,1H), 3.47(s,3H).

[0825] Example 59

[0826] 5-Bromo-2-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0827]

[0828] Et3N (101 μL, 0.72 mmol) and TBAF (18 μL, 0.018 mmol in 1 M THF) were added 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), and the mixture was stirred at 50 °C for 5 h. The mixture was filtered, concentrated, and purified by preparative HPLC (C10-C20). 18 H2O / MeCN / 0.1% TFA) to provide the title compound (63 mg, 65%). ESI-MS m / z, for [C 19 H 19 BrN6O4S2][M+H] + Calculated value: 539.0; Measured value: 539.0. 1 H NMR (500MHz, methanol-d4) δ8.79-8.37(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=5.9Hz,1H),4.37-4.19(m,1H),3.73(dd,J=11.4,5.4Hz,1H),3.68(dd,J=11.4,6.6Hz,1H),3.48(s,3H).

[0829] Example 60

[0830] 5-Bromo-2-(N-methyl-carbonyl)phenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0831]

[0832] DIPEA (0.12 mL, 0.67 mmol) was added to a solution of 5-bromo-2-(N-methyl-carbonyl)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), and the mixture was stirred at 50 °C for 3 h. The mixture was then purified by preparative HPLC (C10-C2 ... 18 H2O / MeCN / 0.1% TFA) to provide the title compound (89 mg, 67%). ESI-MS m / z, for [C 20 H 21 BrClN5O5S2][M+H] + Calculated value: 590.0; Measured value: 590.0. 1 H NMR (500MHz, methanol-d4) δ8.61(s,1H),8.00(d,J=1.9Hz,1H),7.56(dd,J=8.2,1.9Hz,1H ),7.46(s,1H),7.32(d,J=8.2Hz,1H),6.18(d,J=5.3Hz,1H),5.05(dd,J=11.4,2.9H z,1H),4.60(dd,J=11.4,5.4Hz,1H),4.49(t,J=6.4Hz,1H),4.20(d,J=2.1Hz,1H),3 .73(dd,J=11.4,5.6Hz,1H),3.69(dd,J=11.4,6.7Hz,1H),3.40(s,3H),2.91(s,3H).

[0833] Example 61

[0834] 5-Bromo-2-(N-methyl-carbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0835]

[0836] TFA (0.3 mL) was added to a solution of 5-bromo-2-(N-methyl-carbonyl)phenyl 4,6-O-benzyl-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) at 0 °C and the mixture was stirred overnight at room temperature. Et3N (0.5 mL) was added at 0 °C and the mixture was concentrated. The residue was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to provide the title compound (60.7 mg, 83%). ESI-MS m / z, for [C 20 H 22 BrN5O5S2][M+H] + Calculated value: 556.0; Measured value: 556.0. 1 H NMR (400MHz, methanol-d4) δ8.61 (s, 1H), 8.03 (d, J = 2.0Hz, 1H), 7.91 (d, J = 3.2Hz, 1H), 7.66(d,J=3.2Hz,1H),7.58(dd,J=8.0,2.0Hz,1H),7.34(d,J=8.0Hz,1H),6.20(d ,J=5.2Hz,1H),5.08(dd,J=11.2,2.8Hz,1H),4.62(dd,J=11.2,5.2Hz,1H),4.51( t,J=6.0Hz,1H),4.25-4.20(m,1H),3.79-3.66(m,2H),3.41(s,3H),2.93(s,3H).

[0837] Example 62

[0838] 5-Chloro-2-(N-methyl-carbonyl)phenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0839]

[0840] TFA (0.3 mL) was added to a solution of 5-chloro-2-(N-methyl-carbonyl)phenyl 4,6-O-benzyl-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) at 0 °C and the mixture was stirred overnight at room temperature. Et3N (0.5 mL) 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, UV 254] to provide the title compound (60 mg, 59%). ESI-MS m / z, for [C 20 H 22 ClN5O5S2][M+H] + Calculated value: 512.1; Measured value: 512.0. 1 ¹H NMR (400MHz, 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).

[0841] Example 63

[0842] 5-Bromo-2-cyanophenyl-3-deoxy-3-[4-(4-methylthiazolyl-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0843]

[0844] TFA (0.32 mL) was added to a solution of 5-bromo-2-cyanophenyl 4,6-O-benzyl-3-deoxy-3-[4-(4-methylthiazolyl-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) at 0 °C and the mixture was stirred overnight at room temperature. Et3N (0.5 mL) 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, UV 254] to provide the title compound (40.1 mg, 52%). ESI-MS m / z, for [C 20 H 20 BrN5O4S2][M+H] + Calculated value: 538.0; Measured value: 538.0. 1 ¹H NMR (400MHz, 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 = 5.2Hz, 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).

[0845] Example 64

[0846] 5-Bromo-2-cyanopyridin-3-yl-3-[4-(5-chloro-4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0847]

[0848] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-O-benzyl-3-[4-(5-chloro-4-methylthiazo-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 room temperature. Et3N 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 provide the title compound (52.5 mg, 55%). ESI-MS m / z, for [C 19 H 18 BrClN6O4S2][M+H] + Calculated value: 573.0; Measured value: 573.0. 1 H NMR (400MHz, methanol-d4) δ8.71(d,J=2.0Hz,1H),8.62(d,J=2.0Hz,1H),8.59(s,1H),6.50(d,J=5.2Hz,1H),5.12(dd,J=11.2,2.8Hz, 1H), 4.70 (dd, J = 11.2, 5.2Hz, 1H), 4.40 (t, J = 6.0Hz, 1H), 4.20 (d, J = 2.4Hz, 1H), 3.68 (d, J = 6.0Hz, 2H), 3.46 (s, 3H), 2.41 (s, 3H).

[0849] Example 65

[0850] 5-Bromo-2-cyanophenyl 3-[4-(5-chloro-4-methylthiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0851]

[0852] TFA (0.32 mL) was added to a solution of 5-bromo-2-cyanophenyl 4,6-O-benzyl-3-[4-(5-chloro-4-methylthiazolyl-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) at 0 °C and the mixture was stirred overnight at room temperature. Et3N (0.5 mL) 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, UV 254] to provide the title compound (32 mg, 39%). ESI-MS m / z, for [C 20 H 19 BrClN5O4S2][M+H] + Calculated value: 572.0; Measured value: 572.0. 1 ¹H NMR (400MHz, 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).

[0853] Example 66

[0854] 2,5-Dichlorophenyl 3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0855]

[0856] TFA (0.4 mL) was added to a solution of 2,5-dichlorophenyl 4,6-O-benzyl-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) at 0 °C and the mixture was stirred overnight at room temperature. Et3N (0.5 mL) 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, UV 254] to provide the title compound (72 mg, 71%). ESI-MS m / z, for [C 18 H 18 Cl2N4O4S2][M+H] + Calculated value: 489.0; Measured value: 489.0. 1 H NMR (400MHz, methanol-d4) δ8.86(s,1H),8.14(d,J=3.2Hz,1H),8.09(d,J=2.4Hz,1H),7. 89(d,J=3.2Hz,1H),7.70(d,J=8.4Hz,1H),7.54(dd,J=8.4,2.4Hz,1H),6.57(d,J= 5.2Hz, 1H), 5.36 (dd, J=11.2, 2.8Hz, 1H), 4.92 (dd, J=11.2, 5.2Hz, 1H), 4.67 (t, J= 6.0Hz,1H),4.50-4.45(m,1H),4.00-3.91(m,1H),3.91-3.83(m,1H),3.68(s,3H).

[0857] Example 67

[0858] 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

[0859]

[0860] TFA (0.75 mL) was added to a solution of 5-bromo-2-chlorophenyl 4,6-O-benzyl-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), and the mixture was stirred overnight at room temperature. Et3N (1.5 mL) 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, UV 254] to provide the title compound (75 mg, 49%). ESI-MS m / z, for [C 18 H 18 BrClN4O4S2][M+H] + Calculated value: 535.0; Measured value: 535.0. 1 H NMR (400MHz, methanol-d4) δ8.61(s,1H),7.98(d,J=2.0Hz,1H),7.89(d,J=3.2Hz,1H),7.64(d,J=3.2Hz,1H),7.45-7.37(m,2H),6.31(d,J=5.2Hz,1 H), 5.11 (dd, J = 11.2, 3.2Hz, 1H), 4.67 (dd, J = 11.2, 5.2Hz, 1H), 4.43 (t, J = 6.4Hz, 1H), 4.23 (d, J = 2.4Hz, 1H), 3.73-3.60 (m, 2H), 3.31 (s, 3H).

[0861] Example 68

[0862] 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

[0863]

[0864] A solution of 5-chloro-2-fluorophenyl 4,6-O-benzyl-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 overnight at room temperature. Et3N 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, UV 254] to provide the title compound (76.7 mg, 51%). ESI-MS m / z, for [C 18 H 18 ClFN4O4S2][M+H] + Calculated value: 473.0; Measured value: 473.2. 1 H NMR (400MHz, methanol-d4) δ8.61 (s, 1H), 7.89 (d, J = 3.2Hz, 1H), 7.76 (dd, J = 6.4, 2.8Hz, 1H), 7.64(d,J=3.2Hz,1H),7.41-7.32(m,1H),7.18(t,J=8.8Hz,1H),6.23(d,J=5.8Hz,1H) ,5.11(dd,J=11.2,2.8Hz,1H),4.64(dd,J=11.2,5.2Hz,1H),4.48-4.40(m,1H),4.25- 4.20(m,1H),3.68(dd,J=11.2,6.0Hz,1H),3.58(dd,J=11.2,6.0Hz,1H),3.43(s,3H).

[0865] Example 69

[0866] 5-Bromo-2-fluorophenyl 3-deoxy-3-[4-(4-methylthiazolyl-2-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0867]

[0868] TFA (0.40 mL) was added to a solution of 5-bromo-2-fluorophenyl 4,6-O-benzyl-3-deoxy-3-[4-(4-methylthiazolyl-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), and the mixture was stirred overnight at room temperature. Et3N (0.5 mL) 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, UV 254] to provide the title compound (63.4 mg, 67%). ESI-MS m / z, for [C 19 H 20 BrFN4O4S2][M+H] + Calculated value: 531.0; Measured value: 531.0. 1 H NMR (400MHz, methanol-d4) δ8.60 (s, 1H), 7.91 (dd, J = 6.4, 2.4Hz, 1H), 7.57-7.49 (m, 1 H),7.23-7.18(m,1H),7.14(t,J=8.8Hz,1H),6.23(d,J=5.2Hz,1H),5.12(dd,J =11.2,2.8Hz,1H),4.64(dd,J=11.2,5.2Hz,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).

[0869] Example 70

[0870] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-chlorothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0871]

[0872] 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), Et3N (3 mL), and water (1 mL) was stirred overnight at room temperature. 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, UV 254] to provide the title compound (47.9 mg, 67%). ESI-MS m / z, for [C 17 H 14 Cl2N6O4S2][M+H] + Calculated value: 501.0; Measured value: 501.0. 1 H NMR (400MHz, methanol-d4) δ8.46(d,J=2.0Hz,1H),8.35(d,J=2.0Hz,1H),8.33(s,1H),7.77(s,1H),6.13(d,J=5.0Hz,1H),5.00( dd, J=11.2, 2.8Hz, 1H), 4.90 (dd, J=11.2, 5.2Hz, 1H), 4.27 (t, J=6.0Hz, 1H), 4.12 (d, J=2.0Hz, 1H), 3.57 (d, J=6.0Hz, 2H).

[0873] Example 71

[0874] 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

[0875]

[0876] TFA (0.54 mL) was added to a solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzyl-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), and the mixture was stirred at room temperature for 6 h. 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, UV 254] to provide the title compound (45 mg, 62%). ESI-MS m / z, for [C 19 H 19 ClN6O4S2][M+H] + Calculated value: 495.1; Measured value: 495.2. 1 H NMR (400MHz, methanol-d4) δ8.60(d,J=2.4Hz,1H),8.59(s,1H),8.46(d,J=2.4Hz,1H),7. 89(d,J=3.2Hz,1H),7.64(d,J=3.6Hz,1H),6.48(d,J=5.2Hz,1H),5.13(dd,J=11.2, 2.8Hz,1H),4.79(dd,J=11.2,5.2Hz,1H),4.39(t,J=6.0Hz,1H),4.21(d,J=2.4Hz,1 H), 3.91-3.84 (m, 1H), 3.67 (t, J = 6.0Hz, 2H), 3.51-3.44 (m, 1H), 1.07-1.03 (m, 3H).

[0877] Example 72

[0878] 5-Chloro-2-cyanopyridin-3-yl-3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0879]

[0880] TFA (0.79 mL) was added to a solution of 5-chloro-2-cyanopyridin-3-yl 4,6-O-benzyl-3-{4-[2-(di-tert-butoxycarbonylamino)thiazolyl-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), and the mixture was stirred at room temperature for 6 h. 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, UV 254] to provide the title compound (26.5 mg, 56%). ESI-MS m / z, for [C 19 H 20 ClN7O4S2][M+H] + Calculated value: 510.1; Measured value: 510.2. 1 H NMR (400MHz, methanol-d4) δ8.59(d,J=2.0Hz,1H),8.46(d,J=2.0Hz,1H),8.25(s, 1H),6.96(s,1H),6.46(d,J=5.2Hz,1H),5.05(dd,J=11.2,2.8Hz,1H),4.73 (dd,J=11.6,5.6Hz,1H),4.37(t,J=6.0Hz,1H),4.19(d,J=2.4Hz,1H),3.89 -3.82(m,1H),3.66(d,J=6.0Hz,2H),3.48-3.42(m,1H),1.06-1.03(m,3H).

[0881] Example 73

[0882] 5-Chloro-2-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0883]

[0884] TFA (0.40 mL) was added to a solution of 5-chloro-2-cyanophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (62 mg, 0.11 mmol) in DCM (4 mL), and the mixture was stirred at room temperature for 2 h. Et3N (1 mL) 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, UV 254] to provide the title compound (17 mg, 32%). ESI-MS m / z, for [C 19 H 19 ClN6O4S2][M+H] + Calculated value: 495.1; Measured value: 495.2. 1 H NMR (400MHz, methanol-d4) δ8.25(s,1H),7.99(d,J=2.0Hz,1H),7.75(d,J=4.4Hz,1H),7.49(dd,J=8.4,2.0Hz,1H),6.96(s,1H),6.39(d,J=5.2Hz,1 H), 5.03 (dd, J = 11.2, 2.8Hz, 1H), 4.62 (dd, J = 11.2, 5.2Hz, 1H), 4.42 (t, J = 6.0Hz, 1H), 4.20 (d, J = 2.4Hz, 1H), 3.71-3.61 (m, 2H), 3.44 (s, 3H).

[0885] Example 74

[0886] 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0887]

[0888] 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), Et3N (1 mL), and water (0.5 mL) was stirred overnight at room temperature. 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, UV 254] to provide the title compound (5.4 mg, 45%). ESI-MS m / z, for [C 19 H 19 ClN8O4S2][M+H] + Calculated value: 523.1; Measured value: 523.2. 1 H NMR (400MHz, DMSO-d6) δ12.85-12.73(m,1H),8.45(d,J=2.0Hz,1H),8.28(d,J=2.0Hz,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=5.2Hz,1H),5.9 3(d,J=5.2Hz,1H),5.47(d,J=6.8Hz,1H),4.93-4.85(m,1H),4.83-4.73(m,1H),4.64(t,J= 5.6Hz,1H),4.15(t,J=6.4Hz,1H),4.03-3.97(m,1H),3.60-3.50(m,1H),3.45-3.35(m,1H).

[0889] Example 75

[0890] 5-Chloro-2-(1H-imidazol-2-yl)pyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazo-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0891]

[0892] Add 4-(2-trimethylsilylethynyl)thiazolyl-2-yl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (80 mg, 0.20 mmol) to a solution of 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl-azido-3-deoxy-1-thio-α-D-galactopyranoside (80 mg, 0.20 mmol), copper(II) sulfate pentahydrate (50.1 mg, 0.20 mmol), sodium (+)-L-ascorbic acid (39.7 mg, 0.20 mmol), CsF (30.5 mg, 0.20 mmol), and N,N,N',N'-tetramethylethylenediamine (60 μL, 0.40 mmol) to a solution of 5-chloro-2-(1H-imidazol-2-yl)pyridin-3-yl-azido-3-deoxy-1-thio-α-D-galactopyranoside (4 mL) in DMF (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 stir the mixture at room temperature 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, UV 254) to provide the title compound (1.65 mg, 2%). ESI-MS m / z, for [C 19 H 18 ClN7O5S2][M+H] + Calculated value: 524.0; Measured value: 524.0. 1 ¹H 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).

[0893] Example 76

[0894] 5-Chloro-2-(pyridin-2-yl)-pyridin-3-yl 3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0895]

[0896] A solution of 5-chloro-2-(pyridin-2-yl)-pyridin-3-yl 4,6-O-benzyl-3-[4-(4-chlorothiazo-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 room temperature for 6 h. Et3N 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 provide the title compound (9.1 mg, 29%). ESI-MS m / z, for [C 22 H 20 Cl2N6O4S2][M+H] + Calculated value: 567.0; Measured value: 567.0. 1 H NMR (400MHz, methanol-d4) δ8.68-8.66(m,1H),8.56(s,1H),8.51(d,J=2.0Hz,1H),8. 44(d,J=2.4Hz,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=5.2Hz,1H),4.98-4.92(m,1H),4.59(dd,J=11.6,5.2Hz,1H ), 4.28 (t, J = 6.0Hz, 1H), 4.11 (d, J = 2.0Hz, 1H), 3.70-3.62 (m, 2H), 3.18 (s, 3H).

[0897] Example 77

[0898] 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

[0899]

[0900] 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), Et3N (0.8 mL), and water (0.5 mL) was stirred overnight at room temperature. 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, UV 254] to provide the title compound (36 mg, 83%). ESI-MS m / z, for [C 18 H 17 ClN6O4S2][M+H] + Calculated value: 481.0; Measured value: 481.0. 1 H NMR (400MHz, DMSO-d6) δ8.72(s,1H),8.49-8.44(m,1H),8.23-8.18(m,1H),7.79(s,1H),6.13(dd,J=17.2,4.4Hz,2H),5.50(d,J=6.8Hz, 1H),5.00-4.87(m,2H),4.70(t,J=5.6Hz,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).

[0901] Example 78

[0902] 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

[0903]

[0904] 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), 4-(2-trimethylsilylethynyl)thiazol-2-amine (25 mg, 0.13 mmol), copper(II) sulfate pentahydrate (10.6 mg, 0.042 mmol), and (+)-L-ascorbic acid sodium (8 mg, 0.042 mmol) were added and the mixture was stirred at room temperature for 4 h. 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, UV 254) to provide the title compound (11.4 mg, 24%). ESI-MS m / z, for [C 19 H 18 Cl2F3N5O4S2][M+H] + Calculated value: 572.0; Measured value: 572.1. 1 ¹H NMR (400MHz, methanol-d⁴) δ 8.28 (s, 1H), 7.82 (d, J = 2.0Hz, 1H), 7.55–7.48 (m, 2H), 8.95 (s, 1H), 6.13 (d, J = 4.8Hz, 1H), 5.08–5.03 (m, 2H), 4.49 (t, J = 6.0Hz, 1H), 4.19–4.12 (m, 2H), 3.97–3.92 (m, 1H), 3.73–3.64 (m, 2H).

[0905] Example 79

[0906] 3,4-Dichlorophenyl 3-deoxy-2-O-(2,2,2-trifluoroethyl)-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0907]

[0908] 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), 4-(2-trimethylsilylethynyl)thiazol-2-amine (25 mg, 0.13 mmol), copper(II) sulfate pentahydrate (10.6 mg, 0.042 mmol), and (+)-L-ascorbic acid sodium (8 mg, 0.042 mmol) were added and the mixture was stirred at room temperature for 4 h. 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, UV 254) to provide the title compound (8.9 mg, 18%). ESI-MS m / z, for [C 19 H 17 Cl2F3N4O5S2][M+H] + Calculated value: 573.0; Measured value: 573.0. 1 ¹H NMR (400MHz, 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).

[0909] Example 80

[0910] 5-Ethynylpyridin-3-yl-3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0911]

[0912] KF (13.1 mg, 0.23 mmol) was added 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), and the mixture was stirred at room temperature for 30 min. Et3N (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, UV 254) to provide the title compound (42 mg, 60%). ESI-MS m / z, for [C 18 H 16 ClN5O4S2][M+H] + Calculated value: 466.0; Measured value: 466.2. 1 H NMR (400MHz, methanol-d4) δ8.68(d,J=2.0Hz,1H),8.59(s,1H),8.52(d,J=2.0Hz,1H),8.16(t,J=2.0Hz,1H),7.46(s,1H),5.88(d,J =5.2Hz,1H),5.10-5.02(m,1H),4.96-4.87(m,1H),4.48(t,J=6.4Hz,1H),4.24-4.18(m,1H),3.84(s,1H),3.76-3.62(m,2H).

[0913] Example 81

[0914] 5-Ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0915]

[0916] TFA (1.0 mL) was added to a solution of 5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 4,6-O-benzyl-3-{4-[2-(di-tert-butoxycarbonylamino)thiazolyl-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), and the mixture was stirred overnight at room temperature. Et3N (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 room temperature 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, UV 254) to provide the title compound (45 mg, 73%). ESI-MS m / z, for [C 19 H 20 N6O4S2][M+H] + Calculated value: 461.1; Measured value: 461.2. 1 H NMR (400MHz, methanol-d4) δ8.70(d,J=2.0Hz,1H),8.53(d,J=2.0Hz,1H),8.24(s,1H),8.19(t,J=2.0Hz,1H),6.95(s,1H),6.23(d,J=5.2Hz,1H),5.01 (dd,J=11.2,2.8Hz,1H),4.57(dd,J=11.2,5.2Hz,1H),4.45(dd,J=7.2,5.6Hz,1H),4.18(dd,J=2.8,1.2Hz,1H),3.74-3.60(m,2H),3.39(s,3H).

[0917] Example 82

[0918] 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

[0919]

[0920] TFA (0.25 mL) was added to a solution of 5-cyanopyridin-3-yl 4,6-O-benzyl-3-[4-(4-chlorothiazo-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), and the mixture was stirred overnight at room temperature. Et3N (0.5 mL) 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, UV 254] to provide the title compound (48 mg, 63%). ESI-MS m / z, for [C 18 H 17 ClN6O4S2][M+H] + Calculated value: 481.0; Measured value: 481.0. 1 H NMR (400MHz, methanol-d4) δ8.95(d,J=2.0Hz,1H),8.80(d,J=2.0Hz,1H),8.63(s,1H),8.50(t,J=2.0Hz,1H),7.46(s,1H),6.35(d,J=5.2Hz ,1H),5.10(dd,J=11.2,2.8Hz,1H),4.70-4.61(m,1H),4.43(t,J=6.0Hz,1H),4.21-4.16(m,1H),3.68(d,J=6.0Hz,2H),3.41(s,3H).

[0921] Example 83

[0922] 5-Cyanopyridin-3-yl-3-deoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside

[0923]

[0924] A solution of 5-cyanopyridin-3-yl 4,6-O-benzyl-3-deoxy-3-[4-(2-hydroxythiazo-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 room temperature for 3 h, and then Et3N 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, UV 254] to provide the title compound (15.8 mg, 38%). ESI-MS m / z, for [C 18 H 18 N6O5S2][M+H] + Calculated value: 463.1; Measured value: 463.0. 1 H NMR (400MHz, methanol-d4) δ8.95(d,J=2.0Hz,1H),8.79(d,J=2.0Hz,1H),8.49(t,J=2.0Hz,1H),8.31(s,1H),6.68(s,1H),6.33(d,J=5.2Hz,1H),5 .03(dd,J=11.2,2.8Hz,1H), 4.58(dd,J=11.2,5.2Hz,1H), 4.42(t,J=6.0Hz,1H), 4.16(d,J=3.6Hz,1H), 3.68(d,J=6.0Hz,2H), 3.39(s,3H).

[0925] Example 84

[0926] 2-Cyano-5-ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0927]

[0928] 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)thiazo-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 room temperature for 1 h. The reaction was neutralized with Et3N, concentrated, and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254]. The obtained material was stirred at room temperature for 15 min in MeOH (5 mL) and a catalytic amount of NaOMe. 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, UV 254] to provide the title compound (19.6 mg, 51%). ESI-MS m / z, for [C 19 H 17 N7O4S2][M+H + Calculated value: 472.1; Measured value: 472.2. 1 HNMR (400MHz, methanol-d4) δ8.60(d,J=2.0Hz,1H),8.40(d,J=2.0Hz,1H),8.24(s,1H),6.95(s,1H),6.18(d,J=5.2Hz,1H),5.05(dd, J=11.2,2.8Hz,1H),4.94(dd,J=11.2,5.2Hz,1H),4.35(dd,J=6.8,5.2Hz,1H),4.20(dd,J=2.8,1.2Hz,1H),3.71-3.58(m,2H).

[0929] Example 85

[0930] 2-Cyano-5-ethynylpyridin-3-yl-3-[4-(2-aminothiazo-4-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0931]

[0932] TFA (0.97 mL) was added to a solution of 2-cyano-5-(2-trimethylsilyl-1-ethynyl)pyridin-3-yl 4,6-O-benzyl-3-{4-[2-(di-tert-butoxycarbonylamino)thiazo-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), and the mixture was stirred overnight at room temperature. Et3N (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 room temperature 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, UV 254] to provide the title compound (27 mg, 43%). ESI-MS m / z, for [C 20 H 19 N7O4S2][M+H + Calculated value: 486.1; Measured value: 486.2. 1 H NMR (400MHz, methanol-d4) δ8.64(d,J=2.0Hz,1H),8.43(d,J=2.0Hz,1H),8.25(s,1H),6.96(s,1H),6.47(d,J=5.2Hz,1H),5.06(dd ,J=11.2,2.8Hz,1H),4.64(dd,J=11.2,5.2Hz,1H),4.39(t,J=6.0Hz,1H),4.22-4.16(m,1H),3.72-3.59(m,2H),3.44(s,3H).

[0933] Example 86

[0934] 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

[0935]

[0936] A solution of 5-bromo-2-cyanopyridin-3-yl 4,6-O-benzyl-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 room temperature for 1 h, and then Et3N 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 provide the title compound (45.4 mg, 62%). ESI-MS m / z, for [C 19 H 18 BrClN6O4S2][M+H] + Calculated value: 573.0; Measured value: 573.0. 1 H NMR (400MHz, methanol-d4) δ8.70(d,J=2.0Hz,1H),8.64(s,1H),8.61(d,J=2.0Hz,1H ),7.46(s,1H),6.46(d,J=5.2Hz,1H),5.12(dd,J=11.2,2.8Hz,1H),4.80(dd, J=11.2,5.2Hz,1H),4.40(t,J=6.0Hz,1H),4.21(dd,J=2.8,1.2Hz,1H),3.92- 3.80(m,1H),3.68(d,J=6.0Hz,2H),3.52-3.39(m,1H),1.05(t,J=6.8Hz,3H).

[0937] Example 87

[0938] 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

[0939]

[0940] A solution of 3,4-dichlorophenyl 3-[4-(2-aminothiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-4,6-O-benzyl-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 room temperature, and then Et3N 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, UV 254] to provide the title compound (49 mg, 59%). ESI-MS m / z, for [C 19 H 21 Cl2N5O4S2][M+H] + Calculated value: 518.0; Measured value: 518.2. 1 H NMR (400MHz, methanol-d4) δ8.23(s,1H),7.79(d,J=2.0Hz,1H),7.52(dd,J=8.4,2.0H z,1H),7.47(d,J=8.4Hz,1H),6.95(s,1H),6.13(d,J=5.2Hz,1H),4.98(dd,J=1 1.2, 2.8Hz, 1H), 4.64 (dd, J=11.2, 5.2Hz, 1H), 4.43 (t, J=6.4Hz, 1H), 4.18 (dd, J=2.8,1.2Hz,1H),3.84-3.55(m,3H),3.46-3.35(m,1H),1.01(t,J=6.8Hz,3H).

[0941] Example 88

[0942] 3-Chloro-4-cyanophenyl 4,6-O-benzyl-3-{4-[2-(di-tert-butoxycarbonylamino)thiazolyl-4-yl]-1H-1,2,3-triazol-1-yl}-3-deoxy-2-O-ethyl-1-thio-α-D-galactopyranoside

[0943]

[0944] A solution of 3-chloro-4-cyanophenyl 4,6-O-benzyl-3-{4-[2-(di-tert-butoxycarbonylamino)thiazolyl-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 overnight at room temperature, followed by the addition of Et3N 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, UV 254] to provide the title compound (30 mg, 47%). ESI-MS m / z, for [C 20 H 21 ClN6O4S2][M+H] + Calculated value: 509.1; Measured value: 509.0. 1 H NMR (400MHz, methanol-d4) δ8.24(s,1H),7.86(d,J=1.6Hz,1H),7.70(d,J=8.4Hz,1H) ,7.65(dd,J=8.4,1.6Hz,1H),6.95(s,1H),6.43(d,J=5.2Hz,1H),5.01(dd,J=1 1.2, 2.8Hz, 1H), 4.69 (dd, J=11.2, 5.2Hz, 1H), 4.32 (t, J=6.0Hz, 1H), 4.17 (dd, J=2.8,1.2Hz,1H),3.83-3.59(m,3H),3.46-3.35(m,1H),0.99(t,J=6.8Hz,3H).

[0945] Example 89

[0946] 3-Chloro-4-cyanophenyl 2,3-dideoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0947]

[0948] 2-Chloro-4-thiazolyl benzyl nitrile (589 mg, 3.47 mmol) was added to a solution of 4,6-di-O-acetyl-3-deoxy-3-[4-(2-hydroxythiazolyl-4-yl)-1H-1,2,3-triazol-1-yl]-D-galactosene (880 mg, 2.31 mmol) and oxotrichloro[(dimethyl sulfide)triphenylphosphine oxide]rhenium (V) (150 mg, 0.23 mmol) in toluene (20 mL), and the mixture was stirred at 70 °C for 20 h. The mixture was evaporated and purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254]. The obtained material was stirred in MeOH (5 mL) and a catalytic amount of NaOMe at room temperature for 1 h. The mixture was neutralized with acidic resin, filtered, concentrated, and purified by preparative SFC to provide the title compound (13.5 mg, 1%). ESI-MS m / z, for [C 18 H 16 ClN5O4S2][M+H] + Calculated value: 466.0; Measured value: 466.0 1 H NMR (400MHz, methanol-d4) δ8.28(s,1H),7.84(d,J=1.6Hz,1H),7.71-7.62(m,2H),6.67(s,1H),6.18(d,J=5.2Hz,1H),5.19-5.14(m,1H), 4.37(t,J=6.0Hz,1H),4.21(dd,J=5.2,2.0Hz,1H),4.15(s,1H),3.73-3.71(m,1H),3.17-3.09(m,1H),2.33(dd,J=13.6,4.4Hz,1H).

[0949] Example 90

[0950] 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

[0951]

[0952] 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), dimethylamine hydrochloride (16.5 mg, 0.20 mmol), HATU (96.2 mg, 0.25 mmol), and DIPEA (87 μL, 0.51 mmol) were added and the mixture was stirred overnight at room temperature. 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, UV 254) to provide the title compound (10 mg, 32%). ESI-MS m / z, for [C 21 H 24 BrClN6O5S2][M+H] + Calculated value: 619.0; Measured value: 619.0. 1 H NMR (400MHz, methanol-d4) δ8.63(d,J=2.0Hz,1H),8.61(s,1H),8.50(d,J=2.0Hz,1 H),7.46(s,1H),6.25(d,J=5.2Hz,1H),5.04(dd,J=11.2,2.8Hz,1H),4.70(dd ,J=11.2,5.2Hz,1H),4.49(t,J=6.0Hz,1H),4.18(d,J=2.8Hz,1H),3.85-3.6 8(m,3H),3.47-3.35(m,1H),3.13(s,3H),2.88(s,3H),1.02(t,J=7.2Hz,3H).

[0953] Example 91

[0954] 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

[0955]

[0956] TFA (0.3 mL) was added to a solution of 5-ethynyl-2-(N,N-dimethylcarbamoyl)pyridin-3-yl 4,6-O-benzyl-3-[4-(4-chlorothiazo-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), and the mixture was stirred overnight at room temperature. Et3N 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, UV 254] to provide the title compound (15 mg, 58%). ESI-MS m / z, for [C 22 H 23 ClN6O5S2][M+H] + Calculated value: 551.1; Measured value: 551.2. 1 ¹H NMR (400MHz, 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).

[0957] Example 92

[0958] 2-(N-azacyclobutylcarbamoyl)-5-ethynylpyridin-3-yl3-[4-(4-chlorothiazol-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0959]

[0960] TFA (0.3 mL) was added to a solution of 2-(N-azacyclobutylcarbamoyl)-5-ethynylpyridin-3-yl 4,6-O-benzyl-3-[4-(4-chlorothiazo-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), and the mixture was stirred overnight at room temperature. Et3N 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, UV 254] to provide the title compound (5 mg, 19%). ESI-MS m / z, for [C 23 H 23 ClN6O5S2][M+H] + Calculated value: 563.1; Measured value: 563.2. 1 HNMR (400MHz, methanol-d4) δ8.63(s,1H),8.55(d,J=1.6Hz,1H),8.36(d,J=1.6Hz,1H),7.47(s,1H),6.34(d,J=5.2Hz,1H),5.11(dd,J=11.2,3.2Hz ,1H),4.64(dd,J=11.2,5.2Hz,1H),4.45(t,J=6.0Hz,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).

[0961] Example 93

[0962] 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

[0963]

[0964] A solution of 5-chloro-2-(N-methylcarbamoyl)pyridin-3-yl 4,6-O-benzyl-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 overnight at room temperature, and then Et3N 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, UV 254] to provide the title compound (13.5 mg, 39%). ESI-MS m / z, for [C 19 H 20 Cl2N6O5S2][M+H] + Calculated value: 547.0; Measured value: 547.1. 1 H NMR (400MHz, methanol-d4) δ8.53(s,1H),8.30(s,2H),7.37(s,1H),6.31(d,J=5.6Hz,1H),5.08(dd,J=11.6,3.2Hz,1H),4.59(dd, J=11.6,5.6Hz,1H),4.27(dd,J=6.8,5.6Hz,1H),4.09(dd,J=3.2,1.2Hz,1H),3.67-3.46(m,2H),3.29(s,3H),2.83(s,3H).

[0965] Example 94

[0966] 5-Chloro-2-(N-ethylcarbamoyl)pyridin-3-yl-3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0967]

[0968] A solution of 5-chloro-2-(N-ethylcarbamoyl)pyridin-3-yl 4,6-O-benzyl-3-[4-(4-chlorothiazo-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 room temperature, followed by the addition of Et3N 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, UV 254] to provide the title compound (40 mg, 49%). ESI-MS m / z, for [C 20 H 22 Cl2N6O5S2][M+H] + Calculated value: 561.0; Measured value: 561.1. 1 H NMR (400MHz, methanol-d4) δ8.63(s,1H),8.40(dd,J=4.4,2.0Hz,2H),7.47(s,1H),6.39(d,J=5.2Hz,1H),5.17(dd,J=11.2,3.2Hz,1H),4.68(dd ,J=11.2,5.6Hz,1H),4.38(t,J=6.0Hz,1H),4.19(d,J=2.4Hz,1H),3.73-3.64(m,2H),3.44-3.20(m,2H),3.38(s,3H),1.25-1.21(m,3H).

[0969] Example 95

[0970] 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

[0971]

[0972] A solution of 5-chloro-2-(N-methylcarbamoyl)pyridin-3-yl 4,6-O-benzyl-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 room temperature, and then Et3N 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, UV 254] to provide the title compound (47.1 mg, 68%). ESI-MS m / z, for [C 20 H 22 Cl2N6O5S2][M+H] + Calculated value: 561.0; Measured value: 561.2. 1 H NMR (400MHz, methanol-d4) δ8.88(s,1H),8.70-8.58(m,2H),7.71(s,1H),6.61(d,J=5.6Hz,1H),5.43(dd,J=11.2,2.8Hz,1H),5.03(dd,J=11 .2,5.6Hz,1H),4.62(t,J=6.0Hz,1H),4.45(d,J=2.0Hz,1H),4.10-3.84(m,3H),3.75-3.63(m,1H),3.17(s,3H),1.26(t,J=6.8Hz,3H).

[0973] Example 96

[0974] 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

[0975]

[0976] 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)ethynyl-trimethyl-silane (57 mg, 0.26 mmol), and K₂CO₃ (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 purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA) to provide the title compound (32 mg, 35%). ESI-MS m / z, for [C 19 H 17 Cl2N5O4S2][M+H] + Calculated value: 514.0; Measured value: 514.0. 1 H NMR (500MHz, methanol-d4) δ8.65 (s, 1H), 8.01 (d, J = 2.0Hz, 1H), 7.77 (d, J = 8.4Hz, 1H), 7.51(dd,J=8.4,2.0Hz,1H),7.47(s,1H),6.41(d,J=5.3Hz,1H),5.12(dd,J=11.3 ,2.9Hz,1H),4.70(dd,J=11.3,5.3Hz,1H),4.45(t,J=6.2Hz,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).

[0977] Example 97

[0978] 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

[0979]

[0980] DIPEA (0.14 mL, 0.81 mmol) was added to a solution of 1,3-benzothiazol-6-yl-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), and the mixture was stirred at 50 °C for 2 h. The mixture was then purified by preparative HPLC (C10-C2 ... 18 H2O / MeCN / 0.1% TFA) to provide the title compound (63 mg, 45%). ESI-MS m / z, for [C 19 H 18 ClN5O4S3][M+H] + Calculated value: 512.0; Measured value: 512.0. 1 HNMR (500MHz, methanol-d4) δ9.26(s,1H),8.64(s,1H),8.40(d,J=1.5Hz,1H),8.03(d,J=8 .5Hz,1H),7.80(dd,J=8.5,1.8Hz,1H),7.47(s,1H),6.18(d,J=5.3Hz,1H),5.10(dd, J=11.4,2.9Hz,1H),4.64(dd,J=11.4,5.3Hz,1H),4.59(t,J=6.3Hz,1H),4.22(d,J= 2.1Hz, 1H), 3.73 (dd, J=11.5, 5.5Hz, 1H), 3.69 (dd, J=11.5, 6.7Hz, 1H), 3.43 (s, 3H).

[0981] Example 98

[0982] 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

[0983]

[0984] DIPEA (0.14 mL, 0.81 mmol) was added to a solution of 1,3-benzothiazo-6-yl-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)thiazo-2-ol (67 mg, 0.34 mmol) in MeCN (2.0 mL), and the mixture was stirred at 50 °C for 3 h. The mixture was then purified by preparative HPLC (C10-C2 ... 18 H2O / MeCN / 0.1% TFA) to provide the title compound (35 mg, 26%). ESI-MS m / z, for [C 19 H 19 [N5O5S3][M+H] + Calculated value: 494.1; Measured value: 494.1. 1 HNMR (500MHz, methanol-d4) δ9.26 (s, 1H), 8.40 (d, J = 1.6Hz, 1H), 8.37 (s, 1H), 8.0 4(d,J=8.5Hz,1H),7.79(dd,J=8.5,1.8Hz,1H),6.71(s,1H),6.16(d,J=5.3H z,1H),5.06(dd,J=11.4,2.9Hz,1H),4.59-4.54(m,2H),4.20(d,J=2.1Hz,1 H), 3.72 (dd, J=11.5, 5.5Hz, 1H), 3.68 (dd, J=11.5, 6.7Hz, 1H), 3.42 (s, 3H).

[0985] Example 99

[0986] 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

[0987]

[0988] DIPEA (0.14 mL, 0.81 mmol) was added to a solution of 1,3-benzothiazo-6-yl-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)thiazo-2-amine (67 mg, 0.34 mmol) in MeCN (2.0 mL), and the mixture was stirred at 50 °C for 2 h. The mixture was then purified by preparative HPLC (C10-C2 ... 18H2O / MeCN / 0.1% TFA) to provide the title compound (96 mg, 72%). ESI-MS m / z, for [C 19 H 20 [N6O4S3][M+H] + Calculated value: 493.1; Measured value: 493.1. 1 HNMR (500MHz, methanol-d4) δ9.28(s,1H),8.59(s,1H),8.42(d,J=1.5Hz,1H),8.06(d,J=8.5Hz,1H),7.81(dd,J=8.5,1. 7Hz,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).

[0989] Example 100

[0990] 5-Cyano-1,3-benzothiazo-6-yl-3-[4-(4-chlorothiazo-2-yl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[0991]

[0992] Et3N (52 μL, 0.38 mmol) and TBAF (9.4 μL, 1 M in THF, 0.0094 mmol) were added to a solution of 5-cyano-1,3-benzothiazo-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-chlorothiazo-2-yl)ethynyltrimethylsilane (30 mg, 0.14 mmol) in MeCN (1.5 mL), and the mixture was stirred at 50 °C for 1 h. The mixture was filtered and purified by preparative HPLC (C10-C2 ... 18 H2O / MeCN / 0.1% TFA) to provide the title compound (43 mg, 48%). ESI-MS m / z, for [C 20 H 17 ClN6O4S3][M+H] + Calculated value: 537.0; Measured value: 537.0. 1H NMR (500MHz, methanol-d4) δ9.41(s,1H),8.67(s,1H),8.65(s,1H),8.53(s,1H),7.47(s,1H),6.35(d,J=5.3Hz,1H),5.16(dd,J=1 1.3, 2.9Hz, 1H), 4.70 (dd, J = 11.3, 5.3Hz, 1H), 4.57 (t, J = 6.1Hz, 1H), 4.23 (d, J = 2.5Hz, 1H), 3.71-3.63 (m, 2H), 3.52 (s, 3H).

[0993] Example 101

[0994] 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

[0995]

[0996] A solution of thiazo[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-chlorothiazo-2-yl)ethynyltrimethylsilane (98 mg, 0.46 mmol) in MeCN (3.0 mL) was mixed with Et3N (0.17 mL, 1.21 mmol) and TBAF (30 μL, 1 M in THF, 0.030 mmol) and stirred at 50 °C for 2.5 h. The mixture was filtered and purified by preparative HPLC (C 18 H2O / MeCN / 0.1% TFA). The obtained product was further purified by chromatography (SiO2, EtOAc / MeOH) to provide the title compound (2.1 mg, 1%). ESI-MS m / z, for [C 18 H 17 ClN6O4S3][M+H] + Calculated value: 513.0; Measured value: 513.0. 1H NMR (500MHz, methanol-d4) δ9.59(s,1H),8.95(d,J=2.1Hz,1H),8.91(d,J=2.0Hz,1H),8.66(s,1H),7.49(s,1H),6.25(d,J=5.3Hz,1H),5.1 5(dd,J=11.4,2.8Hz,1H),4.68(dd,J=11.3,5.2Hz,1H),4.60(t,J=6.0Hz,1H),4.26-4.22(m,1H),3.73(d,J=6.1Hz,2H),3.47(s,3H).

[0997] Example 102

[0998] 5-Methylthioalkylpyridin-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

[0999]

[1000] Sodium methanethiol (33 mg, 0.47 mmol) was added 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), and the mixture was stirred at room temperature for 22 h. The mixture was partitioned between EtOAc and water. The organic phase was dried, evaporated, and purified by preparative HPLC (C1000- ... 18 H2O / MeCN / 0.1% TFA) to provide the title compound (7 mg, 15%). ESI-MS m / z, for [C 18 H 20 ClN5O4S3][M+H] + Calculated value: 502.0; Measured value: 502.0. 1 H NMR (500MHz, methanol-d4) δ8.66(s,1H),8.60(s,1H),8.47-8.43(m,1H),8.25(t,J=2.0Hz,1H),7.49(s,1H),6.36(d,J=5.3Hz,1H),5.12(dd,J= 11.3, 2.9Hz, 1H), 4.68 (dd, J = 11.3, 5.3Hz, 1H), 4.48 (t, J = 6.1Hz, 1H), 4.22 (d, J = 2.3Hz, 1H), 3.76-3.69 (m, 2H), 3.44 (s, 3H), 2.64 (s, 3H).

[1001] Example 103

[1002] 5-(trifluoromethylthioalkyl)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

[1003]

[1004] Et3N (53 μL, 0.38 mmol) and TBAF (9.5 μL, 1 M in THF, 0.0095 mmol) were added to a solution of 5-(trifluoromethylthioalkyl)pyridin-3-yl-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), and the mixture was stirred at 50 °C for 2 h. The mixture was filtered and purified by preparative HPLC (C10-C20). 18 H2O / MeCN / 0.1% TFA) to provide the title compound (38 mg, 72%). ESI-MS m / z, for [C 18 H 17 ClF3N5O4S3][M+H] + Calculated value: 556.0; Measured value: 556.0. 1 H NMR (500MHz, methanol-d4) δ8.93(d,J=2.0Hz,1H),8.74(d,J=1.8Hz,1H),8.66(s,1H) ,8.48(t,J=1.9Hz,1H),7.49(s,1H),6.35(d,J=5.3Hz,1H),5.13(dd,J=11.3,2 .9Hz,1H),4.69(dd,J=11.3,5.3Hz,1H),4.48(t,J=6.2Hz,1H),4.24(d,J=2.4H z, 1H), 3.73 (dd, J = 11.4, 5.4Hz, 1H), 3.67 (dd, J = 11.4, 6.8Hz, 1H), 3.44 (s, 3H).

[1005] Intermediate 1

[1006] (3,5-Dichloro-4-fluorophenyl)thioalkylthiocarboxylic acid-O-ethyl ester

[1007]

[1008] 3,5-Dichloro-4-fluoroaniline (6.70 g, 37.2 mmol) was suspended in HCl / H₂O (V / V = 1:4, 100 mL) and the suspension was cooled to -5 °C. A solution of NaNO₂ (5.14 g, 74.4 mmol) in H₂O (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 H₂O (50 mL). The mixture was stirred at 50 °C for 3 h and then extracted with EtOAc (3 x 100 mL). The combined organic phases were dried over Na₂SO₄, concentrated, and purified by column chromatography (PE, silica-CS 80 g, 40 mL / min, silica gel, UV 254) to give the product (7.30 g, 60%). 1 ¹H NMR (400MHz, methanol-d⁴) δ 7.67 (d, J = 6.3Hz, 2H), 4.66 (q, J = 7.1Hz, 2H), 1.36 (t, J = 7.1Hz, 3H).

[1009] 3,5-Dichloro-4-fluorobenzenethiol

[1010]

[1011] To a solution of (3,5-dichloro-4-fluorophenyl)thioalkylthiocarboxylic acid-O-ethyl ester (7.30 g, 22.3 mmol) in MeOH (50 mL), NaOH (22 mL, 2 M) was added 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 an aqueous solution of NaHSO4 and extracted with EtOAc (100 mL) and diethyl ether (2 x 100 mL). The combined organic phases were dried and evaporated to provide the product (4.60 g, 88%). 1 H NMR (400MHz, DMSO) δ7.58 (d, J=5.0Hz, 2H), 6.03 (s, 1H).

[1012] 2,4,6-Tri-O-acetyl-3-azido-3-deoxy-β-D-galactopyranosylchloride

[1013]

[1014] 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 ether compound (50 μL, 0.41 mmol) in DCM (150 mL) was stirred at room temperature for 1 h. The mixture was partitioned between a saturated aqueous solution of NaHCO3 and DCM. The organic phase was dried, concentrated, and the residue was milled in diethyl ether / PE to provide a product as a crystalline solid (10.2 g, 91%). 1 H NMR (400MHz, chloroform-d) δ5.48(d,J=3.2Hz,1H),5.34(t,J=9.2Hz,1H),5.24(d,J=8.7Hz,1H),4.18(dd,J=11.5,6.1Hz,1H),4 .10(dd,J=11.6,6.7Hz,1H),3.98(t,J=6.4Hz,1H),3.60(dd,J=10.3,3.3Hz,1H),2.20(s,3H),2.17(s,3H),2.07(s,3H).

[1015] 3,5-Dichloro-4-fluorophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside

[1016]

[1017] Cs₂CO₃ (17.3 g, 53.2 mmol) was added to a solution of 2,4,6-tri-O-acetyl-3-azido-3-deoxy-β-D-pyranogalactosyl chloride (6.20 g, 17.7 mmol) and 3,5-dichloro-4-fluorobenzenethiol (3.77 g, 19.1 mmol) in DMF (20 mL), 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 / 1–5 / 1, silica-CS120 g, 40 mL / min, silica gel, UV 254). Further purification by reversed-phase chromatography (MeCN / H₂O = 1 / 20–3 / 1, C-18 column, 20 mL / min, UV 254) yielded the product (2.2 g, 24%). ESI-MS m / z, for [C 18 H 18 Cl2FN3O7S][M+NH4 + Calculated value: 527.0; Measured value: 527.0. 1H NMR (400MHz, CDCl3) δ7.40 (t, J = 18.0Hz, 2H), 5.86 (d, J = 5.5Hz, 1H), 5.41 (d, J = 2.7Hz, 1H), 5.26-5.07 (m, 1H), 4.54 (dd, J = 7. 7,4.6Hz,1H),4.13-4.03(m,1H),4.03-3.90(m,1H),3.84(dd,J=11.0,3.3Hz,1H),2.11(d,J=11.0Hz,6H),2.04-1.90(m,3H).

[1018] 3,5-Dichloro-4-fluorophenyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside

[1019]

[1020] 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 / Et3N / H2O (18 mL, 5:3:1) was stirred overnight at room temperature. The mixture was evaporated and purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3 = 30%–90%, X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to give the product (860 mg, 52%). ESI-MS m / z, for [C 12 H 12 Cl2FN3O4S][M+NH4] + Calculated value: 401.0; Measured value: 401.0. 1 H NMR (400MHz, methanol-d4) δ7.66(d,J=6.3Hz,2H),5.64(d,J=5.5Hz,1H),4.36(dd,J=10.8,5.5Hz,1H) ,4.24(t,J=5.9Hz,1H),4.02(d,J=2.1Hz,1H),3.74-3.60(m,2H),3.47(dd,J=10.8,2.9Hz,1H).

[1021] 3,5-Dichloro-4-fluorophenyl-3-azido-4,6-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside

[1022]

[1023] Benzaldehyde dimethyl acetal (444 mg, 2.92 mmol) was added 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), followed by D(+)-10-camphor sulfonic acid (67.8 mg, 0.29 mmol). The mixture was stirred under vacuum at 50 °C for 3 h using a water pump. The mixture was added dropwise to an aqueous solution of NaHCO3 (100 mL) and the solution was filtered. The resulting white solid was dried under vacuum to provide the product (600 mg, 96%). ESI-MS m / z, for [C 19 H 16 Cl2FN3O4S][M+H] + Calculated value: 472.0; Measured value: 472.0. 1 H NMR (400MHz, methanol-d4) δ7.52(d,J=6.2Hz,2H),7.39(d,J=3.7Hz,2H),7.25(dd,J=5.1,1.9Hz,3H),5.71(d,J=5.2Hz,1H),5.57(s,1H),4.80 (m,1H),4.40(dd,J=10.9,5.1Hz,1H),4.34(d,J=3.0Hz,1H),4.06(d,J=7.6Hz,1H),3.96(d,J=12.6Hz,1H),3.50(dd,J=10.9,3.2Hz,1H).

[1024] 3,5-Dichloro-4-fluorophenyl-3-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[1025]

[1026] To a solution of 3,5-dichloro-4-fluorophenyl-3-azido-4,6-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside (300 mg, 0.64 mmol) in DMF (5 mL), NaH (60% in oil, 73.0 mg, 1.91 mmol) was added. The mixture was stirred for 30 min, and then iodomethane (79.1 μL, 1.27 mmol) was added dropwise. The mixture was stirred at room temperature for 1 h and then poured into water (15 mL). The solution was extracted with EtOAc and the organic phase was evaporated to provide the product (300 mg, 97%). ESI-MS m / z, for [C 20 H 18 Cl2FN3O4S][M+H] +Calculated value: 486.0; Measured value: 486.0. 1 H NMR (400MHz, CDCl3) δ7.45(dd,J=7.5,2.0Hz,2H),7.37(t,J=4.6Hz,2H),7.34-7.25(m,3H),5.91(d,J=5.2Hz,1H),5.56(s,1H) ,4.26(d,J=2.7Hz,1H),4.18(ddd,J=8.0,5.6,3.4Hz,2H),4.12-3.97(m,2H),3.60(dd,J=10.7,3.3Hz,1H),3.50-3.45(m,3H).

[1027] 3,5-Dichloro-4-fluorophenyl 4,6-O-benzyl-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[1028]

[1029] A solution of 3,5-dichloro-4-fluorophenyl-3-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (135 mg, 0.28 mmol) in DMF (5 mL) was mixed with trimethyl(2-thiazolyl-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) and stirred at room temperature for 6 h. The mixture was concentrated and purified by column chromatography (PE / EtOAc = 10 / 0-1 / 1, silica-CS 12 g, 20 mL / min, silica gel, UV 254) to give the product (76 mg, 46%). ESI-MS m / z, for [C 25 H 21 Cl2FN4O4S2][M+H] + Calculated value: 595.0; Measured value: 595.0. 1H NMR (400MHz, DMSO-d6) δ8.82(s,1H),7.89-7.75(m,4H),7.39-7.34(m,5H),6.63(d,J=5.2Hz,1H),5.58(s,1H),5.16(dd,J=11.2,2.8H z, 1H), 4.84 (dd, J = 11.6, 5.2Hz, 1H), 4.58 (d, J = 2.8Hz, 1H), 4.11 (s, 1H), 4.09 (d, J = 12.4Hz, 1H), 3.92 (d, J = 11.6Hz, 1H), 3.34 (s, 3H).

[1030] Intermediate 2

[1031] 5-Bromopyridin-3-yl-2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside

[1032]

[1033] Cs₂CO₃ (4.47 g, 13.7 mol) was added to a solution of 2,4,6-tris-O-acetyl-3-azido-3-deoxy-β-D-pyranogalactosyl chloride (1.20 g, 3.43 mmol) and 5-bromopyridine-3-thiol (1.30 g, 6.86 mol) in DMF (10 mL), and the mixture was stirred overnight at room temperature. The mixture was concentrated and purified by column chromatography (EtOAc / PE = 10%–60%, silica-CS 20 g, 30 mL / min, silica gel, UV 254) to give the product (1.25 g, 72%). ESI-MS m / z, for [C 17 H 19 BrN4O7S][M+H] + Calculated value: 503.0; Measured value: 503.0. 1 H NMR (400MHz, CDCl3) δ8.50(dd,J=10.7,2.0Hz,2H),7.90(t,J=2.0Hz,1H),5.91(d,J=5.5Hz,1H),5.42(d,J=2.7Hz,1H),5.22(dd,J=10. 9,5.5Hz,1H),4.56(dd,J=7.6,4.6Hz,1H),4.15-4.00(m,1H),3.92(ddd,J=14.3,11.3,5.6Hz,2H),2.12(d,J=13.2Hz,6H),1.97(s,3H).

[1034] 5-Bromopyridin-3-yl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside

[1035]

[1036] 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 / Et3N / H2O (0.9 mL, 5:3:1) was stirred at room temperature for 4 h. The mixture was evaporated and purified by preparative HPLC (X-Select 10 μm 19*250 mm, 20 mL / min, MeOH / H2O (10 mmol / L NH4HCO3) = 40%–95%) to provide the product (208 mg, 93%). ESI-MS m / z, for [C 11 H 13 BrN4O4S][M+H] + Calculated value: 377.0, measured value: 377.0. 1 H NMR (400MHz, methanol-d4) δ8.52(d,J=1.8Hz,1H),8.43(d,J=2.0Hz,1H),8.16(t,J=2.0Hz,1H),5.63(d,J=5.4Hz,1H),4.29( dd,J=10.8,5.4Hz,1H),4.15(t,J=6.0Hz,1H),3.95(d,J=2.1Hz,1H),3.61-3.52(m,2H),3.42(dt,J=14.5,7.3Hz,1H).

[1037] 5-Bromopyridin-3-yl-3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[1038]

[1039] D(+)-10-camphorsulfonic acid (25.6 mg, 0.11 mmol) and benzaldehyde dimethyl acetal (168 mg, 1.10 mmol) were added to a solution of 5-bromopyridin-3-yl-azido-3-deoxy-1-thio-α-D-galactopyranoside (208 mg, 0.55 mmol) in DMF (3 mL), and the mixture was stirred under reduced pressure at 50 °C for 5 h. The mixture was partitioned between water (10 mL) and DCM (15 mL). The aqueous phase was extracted with DCM (3 x 5 mL), and the combined organic phases were dried and evaporated. The obtained 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 room temperature for 2 h. Water (10 mL) and DCM (15 mL) were added, and the aqueous layer was extracted with DCM (3 x 5 mL). The combined organic layers were dried over Na₂SO₄, concentrated, and purified by column chromatography (EA / PE = 0-40%, silica-CS 12 g, 20 mL / min, silica gel, UV 254) to give the product (200 mg, 76%). ESI-MS m / z, for [C 19 H 19 BrN4O4S][M+H] + Calculated value: 479.0, measured value: 479.0. 1 H NMR (400MHz, CDCl3) δ8.01-7.90(m,1H),7.51-7.38(m,3H),7.38-7.25(m,4H),5.97(d,J=5.1Hz,1H),5.55(s,1H),4.26( d,J=3.1Hz,1H),4.19(dd,J=10.7,5.1Hz,2H),4.08-4.06(m,1H),4.04(s,1H),3.67-3.63(m,1H),3.50(d,J=5.7Hz,3H).

[1040] 5-Bromopyridin-3-yl4,6-O-benzyl-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[1041]

[1042] Trimethyl(2-thiazo-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) were added to a solution of 5-bromopyridin-3-yl-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (200 mg, 0.42 mmol) in DMF (5 mL), and the mixture was stirred at room temperature for 3 h. The mixture was partitioned between water (10 mL) and DCM (10 mL), and the aqueous phase was extracted with DCM (2 x 5 mL). The combined organic phases were washed with water (20 mL) and brine (20 mL), dried over Na₂SO₄, evaporated, and purified by column chromatography (EA / PE = 10%–70%, silica-CS 4 g, 12 mL / min, silica gel, UV 254) to provide the product (200 mg, 82%). ESI-MS m / z, for [C 24 H 22 BrN5O4S2][M+H] + Calculated value: 588.0, measured value: 588.0. 1 H NMR (400MHz, CDCl3) δ8.39(s,1H),7.96(d,J=8.7Hz,2H),7.64(dt,J=7.2,3.6Hz,1H),7.46(dd,J=5.8,3.3Hz,1H),7.37-7.26(m ,6H),6.12(d,J=4.5Hz,1H),5.46(s,1H),5.31-5.21(m,1H),4.61-4.45(m,2H),4.24(t,J=6.7Hz,2H),4.11(s,1H),3.36(s,3H).

[1043] Intermediate 3

[1044] 3-Azide-4,6-O-benzyl-3-deoxy-D-galactopyranose

[1045]

[1046] A solution of 3-azido-3-deoxy-D-galactopyranose (Lowary, TL; Hindsgaul, O. Recognition of Synthetic O-Methyl, Epimeric, and Amino Analogues of the Acceptor A-L-Fucp-(1→2)-B-D-Galp-or Glycosyltransferases. Carbohydrate Research 1994, 251, 33-67.) (16.4 g, 79.9 mmol) in DMF (120 mL) was mixed with 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 then added dropwise to a saturated aqueous solution of NaHCO3 (200 mL). The mixture was filtered, and the white solid was washed with water and dried under vacuum to provide the product (15.0 g, 64%, α / β = 1:1).

[1047] 3-Azide-4,6-O-benzyl-3-deoxy-α-D-galactopyranose

[1048] 1 H NMR (400MHz, CD3OD) δ7.51-7.53(m,2H),7.35-7.39(m,3H),5.65(s,1H),5.25(d,J=3.2Hz,1H,H-1α),3.35-3.45(m,6H).

[1049] 3-Azide-4,6-O-benzyl-3-deoxy-β-D-galactopyranose

[1050] 1 H NMR (400MHz, CD3OD) δ7.51-7.53 (m, 2H), 7.35-7.39 (m, 3H), 5.65 (s, 1H), 4.58 (d, J = 7.6Hz, 1H, H-1β), 3.35-3.45 (m, 6H).

[1051] Methyl-3-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-D-galactopyranoside

[1052]

[1053] NaH (1.96 g, 51.1 mmol in oil, 60% DMF) was added to a solution of 3-azido-4,6-O-benzyl-3-deoxy-D-galactopyranose (5.00 g, 17.0 mmol) in DMF (40 mL) at 0 °C under a nitrogen atmosphere, and the mixture was stirred for 20 min. Iodomethane (3.18 mL, 51.1 mmol) was added, and the mixture was stirred at room temperature for 1 h. After dilution with water (50 mL), the mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (PE / EtOAc = 10 / 1-1 / 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).

[1054] Methyl-3-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-α-D-galactopyranoside

[1055] 1 H NMR (400MHz, CD3OD) δ7.42-7.44(m,2H),7.27-7.29(m,3H),5.56(s,1H),4.99(d,J=3.2Hz,1 H,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).

[1056] Methyl-3-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-β-D-galactopyranoside

[1057] 1 H NMR (400MHz, CD3OD) δ7.42-7.44(m,2H),7.27-7.29(m,3H),5.55(s,1H),4.31(d,J=7.6Hz,1 H,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).

[1058] Acetyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-D-galactopyranoside

[1059]

[1060] A few drops of concentrated H₂SO₄ were added to a solution of methyl 3-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-D-galactopyranoside (5.10 g, 15.9 mmol) in acetic anhydride (40.0 mL) and acetic acid (20 mL) at 0 °C. The mixture was stirred at 0 °C for 4 h, and then added dropwise to a saturated aqueous solution of NaHCO₃. The mixture was extracted with DCM (3 x 100 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated under vacuum. The residue was purified by column chromatography (PE / EtOAc = 10 / 1-1 / 1, silica-CS 4 g, 12 mL / min, silica gel, UV 254). The obtained 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 while stirring. The mixture was cooled to 0°C and stirred for 1 hour, filtered, and washed with n-heptane / EtOAc (4:1, 10 mL) to give a product (1.2 g) as a white solid, which was used as is in the next step. 1 H NMR(400MHz, CDCl3)δ6.38(d,J=3.6Hz,1H),5.33(dd,J=3.2,1.2Hz,1H),4.14-4.17(m,1H),3.91-4.03(m,2H), 3.80(dd,J=6.4,3.2Hz,1H),3.62(dd,J=10.4,3.6Hz,1H),3.43(s,3H),2.11(s,3H),2.10(s,3H),1.98(s,3H).

[1061] Acetyl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside

[1062]

[1063] PCl5 (1.06 g, 5.08 mmol) was added 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) at 30 °C under a nitrogen atmosphere, followed by the addition of boron trifluoride diethyl ether (0.209 mL, 1.69 mmol). The mixture was stirred at 30 °C for 30 min, then added dropwise to a saturated aqueous solution of NaHCO3. The mixture was extracted with DCM (3 x 100 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under vacuum. 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 room temperature under a nitrogen atmosphere. After dilution with water (50 mL), the mixture was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (PE / EtOAc = 10 / 1-3 / 1, silica-CS 20 g, 18 mL / min, silica gel, UV254) to give the product (1.15 g, 75%, α / β = 0.23:1).

[1064] Acetyl 4,6-di-O-acetyl-3-azido-2-O-methyl-3-deoxy-1-thio-α-D-galactopyranoside

[1065] 1 H NMR (400MHz, CDCl3) δ6.25 (d, J=5.2Hz, 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).

[1066] Acetyl 4,6-di-O-acetyl-3-azido-2-O-methyl-3-deoxy-1-thio-β-D-galactopyranoside

[1067] 1 H NMR (400MHz, CDCl3) δ5.32-5.33(m,1H),5.04(d,J=10.0Hz,1H,H-1β),3.85-4.08(m,3H),3.57(d d,J=9.2,3.2Hz,1H),3.52(s,3H),3.33(t,J=9.6Hz,1H),2.36(s,3H),2.08(s,3H),1.97(s,3H).

[1068] 5-Bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-D-galactopyranoside

[1069]

[1070] Diethylamine (85.0 mg, 1.16 mmol) was added 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-fluoro-pyridin-2-carboxynitrile (175 mg, 0.87 mmol) in DMF (4.0 mL), and the mixture was stirred at room temperature for 1 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by column chromatography (PE / EA = 10 / 1-3 / 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, for [C 17 H 18 BrN5O6S][M+H] + Calculated value: 500.0, measured value: 500.0.

[1071] 5-Bromo-2-cyanopyridin-3-yl4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[1072] 1 H NMR (400MHz, CDCl3) δ8.57-8.58(m,1H),8.13(d,J=2.0Hz,1H),6.05(d,J=5.2Hz,1H),5.35(d,J=3.2Hz ,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).

[1073] 5-Bromo-2-cyanopyridin-3-yl 4,6-di-O-acetyl-3-azido-3-deoxy-2-O-methyl-1-thio-β-D-galactopyranoside

[1074] 1H NMR (400MHz, CDCl3) δ8.57-8.58(m,1H),8.18(d,J=2.0Hz,1H),5.33(dd,J=3.2,1.2Hz,1H),4.68(d,J=9. 2Hz,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).

[1075] 5-Bromo-2-cyanopyridin-3-yl4,6-di-O-acetyl-3-deoxy-2-O-methyl-3-[4-(thiazolyl-2-yl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[1076]

[1077] 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-thiazo-2-ylethynyl)silane (217 mg, 1.20 mmol) in DMF (6.0 mL) was mixed with copper(II) pentahydrate (59.9 mg, 0.24 mmol) and sodium (+)-L-ascorbate (95.0 mg, 0.48 mmol) and stirred at room temperature for 3 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (3 x 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, UV 254). The obtained product was further purified by preparative SFC to obtain the product (57.0 mg, 20%). ESI-MS m / z, for [C 22 H 21 BrN6O6S2][M+H] + Calculated value: 609.0; Measured value: 609.0. 1H NMR (400MHz, CDCl3) δ8.60(d,J=2.0Hz,1H),8.20(d,J=2.0Hz,1H),8.16(s,1 H),7.78(d,J=3.2Hz,1H),7.30(d,J=3.6Hz,1H),6.26(d,J=5.6Hz,1H),5.58( d,J=2.0Hz,1H),4.99(dd,J=11.2,3.2Hz,1H),4.76(dd,J=11.2,5.2Hz,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).

[1078] Intermediate 4

[1079] Acetyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside

[1080]

[1081] A solution of 2,4,6-tris-O-acetyl-3-azido-3-deoxy-β-D-pyranogalactosyl 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 a saturated aqueous solution of NaHCO3 to separate the organic phase, which was then dried and evaporated. The residue was purified by chromatography (SiO2, PE / EtOAc) to provide the product (2.90 g, 52%). ESI-MS m / z, for [C 14 H 19 [N3O8S][M+Na] + Calculated value: 412.1; Measured value: 411.9. 1 ¹H NMR (400MHz, chloroform-d) δ 6.25 (d, J = 5.3Hz, 1H), 5.43 (d, J = 2.9Hz, 1H), 5.40 (dd, J = 11.0, 5.3Hz, 1H), 4.16–3.97 (m, 3H), 3.71 (dd, J = 10.9, 3.3Hz, 1H), 2.43 (s, 3H), 2.16 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H).

[1082] 2-Bromo-5-chloropyridin-3-yl2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside

[1083]

[1084] Diethylamine (488 mg, 6.68 mmol) was added 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), and the mixture was stirred overnight at room temperature. After dilution with water (15 mL), the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA = 10 / 1 to 5 / 1, silica-CS 20 g, 20 mL / min, silica gel, UV 254) to provide a product as a white solid (770 mg, 43%). ESI-MS m / z, for [C 17 H 18 BrClN4O7S][M+H] + Calculated value: 537.0; Measured value: 537.0. 1 H NMR (400MHz, CDCl3) δ8.13(d,J=2.4Hz,1H),7.76(d,J=2.4Hz,1H),6.05(d,J=5.6Hz,1H),5.43(t,J=6.2Hz,1 H), 5.27 (dd, J=11.0, 5.6Hz, 1H), 4.47 (dd, J=7.4, 5.1Hz, 1H), 4.08-4.01 (m, 1H), 3.96 (dq, J=7.9, 5.6Hz, 2H).

[1085] 2-Bromo-5-chloropyridin-3-yl-3-azido-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside

[1086]

[1087] 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 room temperature for 20 min. The mixture was neutralized with an acidic ion exchange 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 under vacuum at 50 °C for 4 h using a water pump. After cooling to room temperature, the mixture was diluted with water (15 mL) and extracted with EtOAc (2 x 10 mL). The combined organic layers were concentrated and purified by column chromatography (PE / EA = 10 / 1-5 / 1, silica-CS 12 g, 20 mL / min, silica gel, UV 254) to give the product (300 mg, 42%). ESI-MS m / z, for [C 18 H 16 BrClN4O4S][M+H] + Calculated value: 499.0, measured value: 499.0. 1 H NMR (400MHz, CDCl3) δ8.09(d,J=2.3Hz,1H),7.82(d,J=2.3Hz,1H),7.45(dd ,J=7.5,1.9Hz,2H),7.38-7.27(m,3H),5.91(d,J=5.3Hz,1H),5.58(s,1H),4 .64(dt,J=10.8,5.4Hz,1H),4.36(d,J=3.0Hz,1H),4.18(dd,J=12.8,1.4Hz, 1H), 4.07-3.97 (m, 2H), 3.65 (dd, J = 10.8, 3.3Hz, 1H), 2.59 (d, J = 5.7Hz, 1H).

[1088] 2-Bromo-5-chloropyridin-3-yl-3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[1089]

[1090] Silver oxide (I) (696 mg, 3.00 mmol) was added to a solution of 2-bromo-5-chloropyridin-3-yl-azido-4,6-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside (300 mg, 0.60 mmol) in DMF (8.0 mL), followed by the addition of methyl iodoform (426 mg, 3.00 mmol). The mixture was stirred at room temperature 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, UV 254) to give the product (240 mg, 78%). ESI-MS m / z, for [C 19 H 18 BrClN4O4S][M+H] + Calculated value: 513.0, measured value: 513.0. 1 H NMR (400MHz, CDCl3) δ8.08(d,J=2.4Hz,1H),7.81(t,J=3.6Hz,1H),7.46(dd,J=7.5,1.9Hz,2H),7.31(ddd,J=6.7,5.1,1.5Hz,3H),6.09(d,J=5.2 Hz,1H),5.56(s,1H),4.28-4.21(m,2H),4.13(dd,J=12.7,1.5Hz,1H),4. 07-4.04(m,1H),3.96(s,1H),3.76(dd,J=10.6,3.3Hz,1H),3.50(s,3H).

[1091] 5-Chloro-2-cyanopyridin-3-yl-3-azido-4,6-O-benzylidene-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside

[1092]

[1093] Zn (14.6 mg, 0.22 mmol), Zn(CN)2 (52.6 mg, 0.45 mmol), 1,1'-bis(diphenylphosphino)ferrocene (20.2 mg, 0.036 mmol) and tris(dibenzylacetone)dipalladium(O) (32.8 mg, 0.036 mmol) were added to a solution of 2-bromo-5-chloropyridin-3-yl-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), and the mixture was stirred at 100 °C for 3 h under a nitrogen atmosphere. The mixture was concentrated and purified by column chromatography (PE / EA = 10 / 1-5 / 1, silica-CS 12 g, 20 mL / min, silica gel, UV 254) to give the product (105 mg, 51%). ESI-MS m / z, for [C 20 H 18 ClN5O4S][M+H] + Calculated value: 460.1, measured value: 460.0. 1 H NMR (400MHz, CDCl3) δ8.44(d,J=2.1Hz,1H),7.98(d,J=2.1Hz,1H),7.46-7.39(m,2H),7.32-7.25(m,3H),6.06(t,J=7.6Hz,1H),5.56(d,J=7.2Hz,1H) ,4.27(t,J=5.2Hz,1H),4.21(dd,J=10.6,5.2Hz,1H),4.12(dd,J=13.0,1. 8Hz, 1H), 4.06 (d, J = 4.4Hz, 2H), 3.71 (dd, J = 10.6, 3.3Hz, 1H), 3.52 (s, 3H).

[1094] 5-Chloro-2-cyanopyridin-3-yl4,6-O-benzyl-3-deoxy-2-O-methyl-3-[4-(2-thiazolyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[1095]

[1096] A solution of 5-chloro-2-cyanopyridin-3-yl-azido-4,6-O-benzyl-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside (130 mg, 0.28 mmol) and trimethyl(2-thiazolyl-2-ylethynyl)silane (103 mg, 0.57 mmol) in DMF (3 mL) was mixed with (+)-L-ascorbic acid sodium (112 mg, 0.57 mmol) and copper(II) sulfate pentahydrate (35.3 mg, 0.14 mmol) and stirred overnight at room temperature. The mixture was evaporated and purified by column chromatography (PE / EA = 10 / 1-5 / 1, silica-CS 4 g, 12 mL / min, silica gel, UV 254) to give the product (90 mg, 56%). ESI-MS m / z, for [C 25 H 21 ClN6O4S2][M+H] + Calculated value: 569.1, measured value: 569.0. 1 H NMR(400MHz, CDCl3)δ8.50(d,J=2.1Hz,1H),8.24(s,1H),8.02(d,J=2.1Hz,1H), 7.78(s,1H),7.32(ddd,J=9.1,7.6,4.0Hz,6H),6.21(d,J=5.1Hz,1H),5.46(s,1 H),5.27(dd,J=11.3,2.7Hz,1H),4.57(dd,J=11.2,5.2Hz,1H),4.52(d,J=2.2Hz ,1H),4.32(s,1H),4.19(d,J=11.8Hz,1H),4.09(d,J=12.0Hz,1H),3.34(s,3H).

[1097] Intermediate 5

[1098] 2-Bromo-5-chloropyridin-3-yl-3-azido-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside

[1099]

[1100] Cs₂CO₃ (1.7 g, 5.0 mmol) was added to a cooled solution (0 °C) of 2-bromo-5-chloropyridin-3-yl-azido-4,6-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside (630 mg, 1.27 mmol) in DMF (10 mL) and the mixture was stirred for 10 min. Benzyl bromide (0.31 mL, 2.54 mmol) was added and the mixture was stirred at room temperature for 2 h. Water (50 mL) was added and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, concentrated, and purified by column chromatography (PE / EtOAc = 10 / 1-5 / 1, silica-CS 12 g, 12 mL / min, silica gel, UV 254) to give the product (460 mg, 62%). ESI-MS m / z, for [C 25 H 22 BrClN4O4S][M+H] + Calculated value: 589.0; Measured value: 589.0. 1 H NMR(400MHz, CDCl3)δ8.07(d,J=2.4Hz,1H),7.61(d,J=2.4Hz,1H)7.45-7.42(m, 2H),7.36-7.29(m,5H),7.26-7.21(m,3H),5.77(d,J=5.2Hz,1H),5.55(s,1H),4 .75(d,J=11.6Hz,1H),4.66(d,J=11.6Hz,1H),4.44(dd,J=5.6,10.8Hz,1H),4.2 8(d,J=2.8Hz,1H),4.12-4.01(m,2H),3.96(s,1H),4.82(dd,J=3.2,10.4Hz,1H).

[1101] 5-Chloro-2-cyanopyridin-3-yl-3-azido-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-α-D-galactopyranoside

[1102]

[1103] Zn (25.4 mg, 0.39 mmol), Zn(CN)2 (182.5 mg, 1.56 mmol), 1,1'-bis(diphenylphosphino)ferrocene (34.6 mg, 0.062 mmol) and tris(dibenzylacetone)dipalladium(O) (28.5 mg, 0.031 mmol) were added to a solution of 2-bromo-5-chloropyridin-3-yl-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). The mixture was stirred at 100 °C for 3 h under a nitrogen atmosphere. The mixture was concentrated and purified by column chromatography (PE / EA = 10 / 1-5 / 1, silica-CS 12 g, 20 mL / min, silica gel, UV 254) to give the product (187 mg, 45%). ESI-MS m / z, for [C 26 H 22 ClN5O4S][M+H] + Calculated value: 536.1; Measured value: 536.0. 1 H NMR (400MHz, chloroform-d) δ8.41 (d, J = 2.4Hz, 1H), 7.65 (d, J = 2.0Hz, 1H), 7.43-7.41 (m,2H),7.39-7.36(m,2H),7.34-7.26(m,6H),5.67(d,J=5.6Hz,1H),5.54(s, 1H),4.81(d,J=11.6Hz,1H)4.64(d,J=11.6Hz,1H),4.40(dd,J=10.8,5.2,1H ), 4.29 (d, J = 3.2Hz, 1H), 4.07 (t, J = 4.0Hz, 3H), 3.78 (dd, J = 10.8, 3.2Hz, 1H).

[1104] 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

[1105]

[1106] A solution of 5-chloro-2-cyanopyridin-3-yl-azido-2-O-benzyl-4,6-O-benzylidene-3-deoxy-1-thio-D-galactopyranoside (75 mg, 0.14 mmol) and trimethyl(2-thiazolyl-2-ylethynyl)silane (38 mg, 0.21 mmol) in DMF (2 mL) was mixed with (+)-L-ascorbic acid sodium (14 mg, 0.07 mmol) and copper(II) sulfate pentahydrate (17.6 mg, 0.07 mmol) and stirred overnight at room temperature. 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, UV 254) to give the product (74.0 mg, 82%). ESI-MS m / z, for [C 31 H 25 ClN6O4S2][M+H] + Calculated value: 645.1, measured value: 645.1. 1 H NMR(400MHz,DMSO-d6)δ8.45(d,J=2.0Hz,1H),8.23(s,1H),7.95(s,1H),7 .67(d,J=2.0Hz,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=10.8Hz,1H),4.76(q,J=11.6,5.2Hz,1H), 4.56-4.44(m,3H),4.31(s,1H),4.17(d,J=12.4Hz,1H),4.09-4.04(m,1H).

[1107] Intermediate 6

[1108] 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

[1109]

[1110] Cesium carbonate (748 mg, 2.30 mmol) was added to a solution of 2-bromo-5-chloropyridin-3-yl-azido-4,6-O-benzyl-3-deoxy-1-thio-α-D-galactopyranoside (620 mg, 1.15 mmol) in DMF (10 mL), followed by the addition of 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 x 50 mL). The organic layer was washed with brine (3 x 50 mL), dried over Na₂SO₄, evaporated, and purified by column chromatography (PE / EA = 10 / 1 to 1 / 1, silica-CS 40 g, 30 mL / min, silica gel, UV 254) to provide the product (700 mg, 79%). ESI-MS m / z, for [C 33 H 28 BrClF2N4O6S][M+H] + Calculated value: 761.1; Measured value: 761.0. 1 ¹H NMR (400MHz, methanol-d⁴) δ 8.09 (d, J = 2.0Hz, 1H), 7.75 (d, J = 2.4Hz, 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 = 5.2Hz, 1H), 5.5 6(s,1H),4.99(s,2H),4.60-4.50(m,2H),4.40(dd,J=10.4,5.2Hz,1H),4.29(d,J=3. 2Hz, 1H), 4.14-4.02 (m, 2H), 3.97 (s, 1H), 3.81 (dd, J = 10.4, 3.2Hz, 1H), 3.72 (s, 3H).

[1111] 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

[1112]

[1113] To a solution of 2-bromo-5-chloropyridin-3-yl-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), 1,1'-bis(diphenylphosphino)ferrocene (103 mg, 0.18 mmol), Zn (89 mg, 0.14 mol), Zn(CN)2 (214 mg, 1.82 mmol), and tris(dibenzylideneacetone)dipalladium(O) (105 mg, 0.18 mmol) were added and the mixture was stirred at 100 °C for 3 h under a nitrogen atmosphere. The mixture was evaporated and purified by column chromatography (DCM / MeOH = 10 / 0–10 / 1, silica-CS 20 g, 20 mL / min, silica gel, UV 254) to give the product (320 mg, 37%). ESI-MS m / z, for [C 34 H 28 ClF2N5O6S][M+NH4 + Calculated value: 725.1, measured value: 725.0. 1 ¹H NMR (400MHz, chloroform-d) δ 8.52 (d, J = 2.4Hz, 1H), 7.96 (d, J = 2.0Hz, 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 = 4.8Hz, 1H), 5.63 (s ,1H),5.08(s,2H),4.72-4.62(m,2H),4.44(dd,J=10.4,4.8Hz,1H),4.39(d,J=3.2Hz, 1H), 4.20-4.10 (m, 2H), 3.86 (dd, J = 10.4, 2.8Hz, 1H), 3.80 (s, 3H), 3.79-3.77 (m, 1H).

[1114] 5-Chloro-2-cyanopyridin-3-yl 4,6-O-benzylene-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

[1115]

[1116] A solution of 5-chloro-2-cyanopyridin-3-yl-azido-4,6-O-benzyl-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 mixed with trimethyl(2-thiazolyl-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 stirred at room temperature for 6...

Claims

1. A D-galactopyranose compound of formula (1) Or its pharmaceutically acceptable salt; in, The pyranose ring is α-D-galactopyranose. A 1 selected from the group consisting of: and , The asterisk * indicates the carbon atom of the heteroaromatic ring covalently linked to the triazole group of formula (1); wherein R 2 selected from halogen; R 3 selected from hydrogen; R 4 selected from OH; R 5 selected from hydrogen; X is selected from S; B 1 Selected from b) phenyl, which is optionally substituted with a group selected from: halogen, CN and C optionally substituted with F. 1-3 alkyl; and d) pyridyl, which is optionally substituted with a group selected from the group consisting of Cl, Br, F, CN; R 1 selected from OC 1-6 alkyl.

2. The compound of claim 1, wherein A 1 is 。 3. The compound of claim 1, wherein A 1 is 。 4. The compound according to claim 1, wherein B1 is a phenyl group substituted with a group selected from the following: Cl; F; Br.

5. The compound of claim 1, wherein R 1 is OCH3.

6. The compound according to claim 1, wherein the compound is selected from the group consisting of:

7. A pharmaceutical composition comprising a compound according to any one of the preceding claims and optionally a pharmaceutically acceptable additive.

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