Novel galactoside inhibitors of galectins

Abstract

The present invention relates to a D-galactopyranose compound of formula (1): [Formula 1] JPEG2022538634000291.jpg3560 The pyranose ring is α-D-galactopyranose, and these compounds have been shown to be effective in treating inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndrome; fibrosis, e.g., pulmonary fibrosis, liver fibrosis, renal fibrosis, ophthalmological fibrosis, and cutaneous and cardiac fibrosis; focal fibrosis such as Dupuytren's disease and Peyronie's disease; fibrotic complications of other treatments such as coronary artery stents, biliary stents, cerebral artery stents, and ureteral stents; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonitis, abnormal scar formation; surgical adhesions; septic shock; cancer, e.g., colorectal cancer, other gastrointestinal cancers, e.g., pancreatic cancer, stomach cancer, biliary tract cancer, lung cancer, mesothelioma, female cancers, e.g., breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube cancer, brain cancer, e.g., medulloblastoma, glioma, meningioma, bone and muscle sarcoma and other sarcomas, leukemia and lymphoma, e.g., T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven bone diseases such as osteogenesis imperfecta; pulmonary hypertension; psoriasis autoimmune diseases such as rheumatoid arthritis, rheumatoid lung disease; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections such as influenza virus, HIV, herpes virus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, e.g., ocular angiogenesis or diseases or conditions associated with ocular angiogenesis, e.g., angiogenesis associated with cancer; and ocular diseases, e.g., age-related macular degeneration and corneal angiogenesis; atherosclerosis; metabolic diseases and uterine diseases such as uterine fibroids and uterine or cervical fibrosis.

Description

[Technical field]

[0001] The present invention relates to novel compounds, their use as medicines and their use for the manufacture of medicines for the treatment of cancer, fibrosis, scars, keloid formation, abnormal scar formation, surgical adhesions, pathological angiogenesis, eye disease, HIV-1 disease, inflammation or transplant rejection in mammals. Furthermore, some compounds have the potential to cross the blood-brain barrier and are potential treatments for CNS conditions. Furthermore, some compounds are suitable as oral drugs. The present invention also relates to pharmaceutical compositions comprising the novel compounds. [Background technology]

[0002] Galectins are proteins with a unique carbohydrate recognition domain (CRD) (Leffler et al. 2004). They are tightly folded β-sandwiches of about 130 amino acids (about 15 kDa) with two defining features: 1) a β-galactose binding site, and 2) sufficient similarity to a sequence motif of about seven amino acids, the majority of which (about six residues) constitutes the β-galactose binding site. However, sites adjacent to the β-galactose site are required for tight binding of natural saccharides, and these different selectivities give galectins different and precise specificities for natural saccharides.

[0003] Recent completion of the human, mouse and rat genome sequences has revealed approximately 15 galectins and galectin-like proteins in one mammalian genome, with slight variations between species (Leffler et al. 2004).

[0004] Galectin subunits can contain either one or two CRDs within a single peptide chain. The first category, mono-CRD galectins, can occur as monomers or dimers (2 species) in vertebrates. The best studied galectins are the dimeric galectin-1 and galectin-3, which are monomers in solution but aggregate into multimers upon association with ligands (Lepur et al. 2012). These were the first galectins to be discovered and are abundant in many tissues.

[0005] Currently, there are more than 5700 publications on galectins in PubMed, mostly on galectin-1 (>1400) and galectin-3 (>2800), as mentioned above. Strong evidence suggests roles for galectins, e.g., in inflammation and cancer, as well as in development (Blidner et al. 2015; Ebrahim et al. 2014).

[0006] Galectins are synthesized as cytosolic proteins without a signal peptide on free ribosomes. Their N-termini are acetylated, a typical modification of cytosolic proteins, and they reside in the cytosol for long periods of time (not typical of secreted proteins). From there, they can be targeted to the nucleus, to specific cytosolic sites, or secreted (inducible or constitutive) by a non-classical (non-ER-Golgi) pathway, which is still unknown, possibly similar to the export of, for example, IL-1 (Leffler et al. 2004; Arthur et al. 2015). Galectins can also function in all these compartments, and for galectin-3, strong evidence published in respected journals supports a role for RNA splicing in the nucleus, inhibition of apoptosis in the cytosol, accumulation around disrupted vesicles, association with microtubules that constitute the core of fibrous tubes, and various extracellular effects on cell signaling and adhesion (Elola et al. 2015, Funasaka et al. 2014, Aits et al. 2015, Clare et al. 2014). Other galectins may also act in the cytosol by enhancing apoptosis and regulating the cell cycle and differentiation of certain cells. Most galectins also act extracellularly by crosslinking glycoproteins (e.g., laminin, integrins, and IgE receptors), possibly forming supramolecularly ordered arrays (Elola et al. 2015), which may thereby regulate cell adhesion and induce intracellular signals. In this context, recent years have seen the emergence of molecular mechanisms of these galectin functions, including the formation of microdomains (lattices) in the membrane that affect intracellular trafficking and cell surface presentation of glycoprotein receptors (Elola et al. 2015). This has been demonstrated in cell cultures, null mutant mice, and animals treated with galectins or galectin inhibitors. (Johannes, L., Jacob, R., Leffler, H. "Galectins at a Glance" J. Cell. Sci. 2018, 131(9), jcs208884).

[0007] Potential therapeutic uses of galectin-3 inhibitors Galectin-3 is involved in diverse phenomena and thus inhibitors may have multiple uses (Blanchard et al. 2014). It is easy to chalk this up to a lack of specificity or lack of scientific focus. Thus, an analogy with aspirin and cyclooxygenases (COX-I and COX-II) is useful. COX generates precursors to a wide range of prostaglandins and is therefore involved in a diverse array of biological mechanisms. Their inhibitors, aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs), also have broad and diverse effects. Nevertheless, these inhibitors are medically very useful and have several different specific utilities.

[0008] Thus, if galectins, like COXs, are part of fundamental biological regulatory mechanisms (which is not yet known), they are likely to be "used intrinsically" for different purposes in different situations. Galectin inhibitors would not be expected to wipe out the entire system like NSAIDs, but would be expected to tip the balance a bit.

[0009] Suppression of inflammation The pro-inflammatory role of galectin-3 is indicated by its induction of cells at inflammatory sites, various effects on immune cells (e.g., oxidative burst in neutrophils and chemotaxis in monocytes), and reduced inflammatory responses, primarily in neutrophils and macrophages, in null mutant mice (Blidner et al. 2015; Arthur et al. 2015). Importantly, recent studies have identified galectin-3 as a critical rate-limiting factor for macrophage M2 differentiation and myofibroblast activation, thus influencing the development of fibrosis (Mackinnon et al. 2008; Mackinnon et al. 2012; Li et al. 2014).

[0010] Inflammation is the body's protective response to invading organisms and tissue damage. However, inflammation, when unbalanced, is often also destructive and occurs as part of the pathology in many diseases. For this reason, there is great medical interest in the pharmacological modulation of inflammation. Galectin-3 inhibitors are expected to provide an important addition to the armamentarium available in this regard.

[0011] Treatment of fibrosis-related diseases Ideas about a possible role of galectin-3 in fibrosis come from cellular and ex vivo studies on macrophage differentiation (Mackinnon et al. 2008) as well as in vivo studies on macrophage differentiation and myofibroblast activation (Mackinnon et al. 2012). Briefly, according to this hypothesis, galectin-3 has been shown to prolong cell surface residence and thus enhance the responsiveness of certain receptors (Elola et al. 2015), for example the TGF-β receptor (MacKinnon, 2012), thereby regulating alternative macrophage differentiation into M2 macrophages and myofibroblast activation.

[0012] Therefore, since galectin-3 is a good candidate as an endogenous enhancer of TGF-β signaling and alternative macrophage differentiation and myofibroblast activation, galectin-3 inhibitors may be very useful for the treatment of fibrosis and adverse tissue remodeling.

[0013] Cancer Treatment Numerous immunohistochemical studies have shown altered expression of specific galectins in cancer (Thijssen et al. 2015; Ebrahim et al. 2014), for example galectin-3 is now an established histochemical marker for thyroid cancer. Direct evidence for the role of galectin-3 in cancer comes mainly from mouse models. In paired tumor cell lines (with decreased or increased expression of galectin-3), induction of galectin-3 leads to more tumors and metastases, whereas inhibition of galectin-3 leads to less tumors and metastases. Galectin-3 has been proposed to enhance tumor growth by being anti-apoptotic, promote angiogenesis, or promote metastasis by affecting cell adhesion. Moreover, recent evidence indicates that galectin-3 plays an important role in the tumor microenvironment (Ruvolo, 2015). Galectin-3 is also thought to regulate interactions between tumor cells and immune cells such as T lymphocytes (T cells), and inhibition of galectin-3 has been shown to restore T cell activity (Demotte et al. 2010, Kouo et al. 2015, Menero et al. 2015). From the above, it is clear that inhibitors of galectin-3 would have beneficial anti-cancer effects. Indeed, saccharides that are said to inhibit galectin-3, but have not been proven to do so, have been reported to have anti-cancer effects. In our own studies, a fragment of galectin-3 containing the CRD inhibited breast cancer in a mouse model by acting as a dominant-negative inhibitor (John et al. 2003). More recently, inhibition of galectin-3 with small molecules has been shown to indeed greatly enhance tumor cell sensitivity to radiation and standard pro-apoptotic agents in cellular assays and ex vivo (Blanchard et al., 2015).

[0014] Also, other galectins are frequently overexpressed in poorly differentiated cancer cells or induced in certain cancer types (Thijssen et al. 2015; Ebrahim et al. 2014). Galectin-1 induces apoptosis in activated T cells and has a prominent immunosuppressive effect on autoimmune diseases in vivo (Blidner et al. 2015). Thus, overexpression of these galectins in cancer may help the tumor defend itself against T cell responses elicited by the host.

[0015] Galectin-1, -3, -7 and -9 null mutant mice have been generated that are healthy and apparently reproduce normally in animal husbandry conditions. However, further studies have revealed subtle phenotypes under different types of challenge, mainly in immune cell function (Blidner et al. 2015) but also in other cell types (Viguier et al. 2014). Due to differences in expression site, specificity and other properties, different galectins cannot functionally replace each other. Observations in null mutant mice would indicate that galectins are not essential for basic life-supporting functions as can be observed under normal animal husbandry conditions. Instead, galectins may be optimizers of normal function and / or essential for stress conditions not seen in animal husbandry conditions. The lack of strong effects in null mutant mice may make galectin inhibitors more favorable as drugs. If galectin activities contribute to pathological conditions as suggested above but not to normal conditions to a great extent, their inhibition would result in fewer unwanted side effects.

[0016] Treatment of Angiogenesis Vascular endothelial growth factor (VEGF), signaling through VEGF receptor 2 (VEGFR-2), is a major angiogenic pathway. Studies have been published showing that both galectin-1 (Gal-1) and galectin-3 (Gal-3) are important modulators of the VEGF / VEGFR-2 signaling pathway (Croci et al. 2014). It has also been published that the galectin inhibitor TDX is expected to have efficacy against pathological angiogenesis (Chen 2012).

[0017] Known inhibitors Natural ligands Several sugars and glycoconjugates capable of binding to galectins have been identified by solid-phase binding and inhibition assays (reviewed by Leffler, 2001 and Leffler et al. 2004). All galectins have a K d It binds to lactose at 1.5 to 1.0 times lower affinity for D-galactose. N-acetyllactosamine and related disaccharides bind similarly to lactose, but for certain galectins they can bind either worse or up to 10 times better. The best small sugar ligands for galectin-3 are those with blood group A determinants attached to lactose or LacNAc residues, which were found to bind approximately 50 times better than lactose. Galectin-1 shows no preference for these sugars.

[0018] Larger saccharides of the polylactosamine type have been proposed as preferred ligands for galectins. In solution, there was evidence of this for galectin-3, but not for galectin-1, using polylactosamine-containing glycopeptides (Leffler and Barondes, 1986). Modified plant pectic polysaccharides have been reported to bind to galectin-3 (Pienta et al. 1995).

[0019] The natural sugars identified as galectin-3 ligands are not suitable for use as active ingredients in pharmaceutical compositions because they are susceptible to acid hydrolysis and enzymatic degradation in the stomach. Furthermore, natural sugars are hydrophilic in nature and are not readily absorbed from the gastrointestinal tract after oral administration.

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

[0021] Synthetic Inhibitors Sugars linked to amino acids with anticancer activity were first identified as natural compounds in serum, but synthetic analogues were subsequently made (Glinsky et al. 1996). Among them, those with lactose or galactose linked to amino acids inhibit galectins, but only approximately as potently as the corresponding underivatized sugars. Chemically modified forms of citrus pectin that inhibit galectin-3 (Platt and Raz, 1992) show antitumor activity in vivo (Pienta et al. 1995; Nangia-Makker et al. 2002).

[0022] Cluster molecules with four or fewer lactose moieties showed strong polyvalent activity when bound to galectin-3, but not to galectin-1 and galectin-5 (Vrasidas et al. 2003). Cyclodextrin-based glycoclusters with seven galactose, lactose, or N-acetyllactosamine residues also showed strong polyvalent activity toward galectin-3, but less so toward galectin-1 and galectin-7 (Andre et al. 2004). Starburst dendrimers (Andre et al. 1999) and glycopolymers (Pohl et al. 1999; David et al. 2004) multivalent with lactose residues have been described as galectin-3 inhibitors with slightly improved efficacy compared to lactose. The above synthetic compounds identified as galectin-3 ligands are not suitable for use as active ingredients in pharmaceutical compositions because they are hydrophilic in nature and are not readily absorbed from the gastrointestinal tract following oral administration.

[0023] The natural oligosaccharides, glycoclusters, glycodendrimers, and glycopolymers mentioned above are too polar and too large to be absorbed and in some cases large enough to cause an immune response in patients. Moreover, they are susceptible to acid and enzymatic hydrolysis in the stomach. Therefore, small synthetic molecules are needed.

[0024] Thiodigalactosides are synthetic, hydrolytically stable, and polar inhibitors known to be nearly as efficient as N-acetyllactosamine (Leffler and Barondes, 1986). N-acetyllactosamine derivatives bearing aromatic amides or substituted benzyl ethers at C-3' have been demonstrated to be highly efficient inhibitors of galectin-3, with unprecedented low IC values ​​of 4.8 μM. 50values, which is a 20-fold improvement compared to the natural N-acetyllactosamine disaccharide (Sorme et al. 2002, Sorme et al. 2003b). These derivatives are less polar overall due to the presence of an aromatic amide moiety and therefore more suitable as inhibitors of galectins in vivo. Furthermore, C3-triazolyl galactosides have been demonstrated to be as potent inhibitors as the corresponding C3-amides of several galectins. Thus, any appropriately structured galactose C3 substituent may confer enhanced galectin affinity.

[0025] However, C3 amide and C3 triazolyl derivatized compounds are susceptible to hydrolysis in vivo due to the presence of glycosidic bonds in the galactose and N-acetyllactosamine sugar moieties, and although they are potent small molecule inhibitors of galectin-3, further improved affinity and stability are desirable. Therefore, inhibitors based on 3,3'-diamide- or 3,3'-ditriazolyl derivatization of thiodigalactosides, which lack the O-glycosidic hydrolytically and enzymatically labile bond, have been developed (Cumpstey et al. 2005b, Cumpstey et al. 2008, Salameh et al. 2010, WO / 2005 / 113569 and US2007185041, WO / 2005 / 113568, US7,638,623B2, T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285). These inhibitors also showed good affinity (down to Kd in the low nM range) for some galectins. Nevertheless, although showing high affinity for galectins, 3,3'-derivatized thiodigalactosides still contain a disadvantage in their multi-step synthesis, which involves a double inversion reaction to reach the 3-N-derivatized galactose building block. Furthermore, cyclohexane substitution of one galactose ring in thiodigalactosides has been shown to mimic the galactose ring and thus provide galectin-1 and galectin-3 inhibitors with efficiencies approaching those of diamide- and ditriazolyl-thiodigalactoside derivatives (WO / 2010 / 126435). Substitution of the D-galactopyranose unit with a substituted cyclohexane reduces polarity and is likely to reduce metabolic sensitivity, thus improving drug-like properties.

[0026] Some of the compounds described above have the following general formula: [ka] and WO / 2005 / 113569. [ka] R I can be D-galactose.

[0027] Recently published US20140099319, WO2014067986 and (T. Delaine, 2016, ChemBioChem 10.1002 / cbic.201600285) describe fluorines (F) on both phenyl rings in the meta position relative to the triazole ring. [ka] This compound has been shown to be a promising drug candidate for pulmonary fibrosis, and is particularly highly selective for galectin-3 with high affinity.

[0028] A series of small C1 or C1 and C3-substituted galactopyranosides have been disclosed that exhibit affinity for galectin-3 and galectin-1. β-D-galactopyranoside has been reported to have affinity in the same range or lower than lactose with a Kd of approximately 91 μM for galectin-3 and 190 μM for galectin-1 (Giguere, D et.al. 2011, 2008, 2006). [ka] The corresponding α-anomers that have better affinity than lactose for galectin-3 or galectin-1 have not been disclosed or described. Summary of the Invention [Means for solving the problem]

[0029] The compounds of the present invention are novel α-D-galactopyranose compounds that unexpectedly show high affinity for galectin-3, some of which are galectin-1 inhibitors, and some of which are combined galectin-1 and galectin-3 inhibitors, and are considered as novel and promising drug candidates. Some of the compounds have good systemic uptake in in vitro and in vivo ADME studies, making them suitable for oral therapy. Some of the compounds also cross the BBB, making them suitable for inhibition of galectins 1 and / or 3 in the CNS.

[0030] In a broad aspect, the present invention provides a D-galactopyranose compound of formula (1): [ka] During the ceremony, The pyranose ring is α-D-galactopyranose, A 1 is R 1 -Z, During the ceremony, Z is a 5-membered heterocycle having at least one heteroatom selected from O, S and N, excluding 1,2,3-triazole, and is linked to α-D-galactopyranose; R 1 a) halogens, CN; -COOH; -CONR 6a R 7a (R 6a and R 7a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6a and R 7a may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F; 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8a R 9a(R 8a and R 9a are independently H, C 1-3 alkyl and isopropyl; OH; and R 10a -CONH-(R 10a is C 1-3 a) aryl, such as phenyl or naphthyl, optionally substituted with a group selected from: alkyl; cyclopropyl; b) halogen; spiroheterocycle; CN; -COOH; -CONR 12a R 13a (R 12a and R 13a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14a R 15a (R 14a and R 15a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl), C(═O)—R 21a (R 21a H and C 1-3 alkyl; OH; and R 16a -CONH-(R 16a is C 1-3 a heterocycle such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl; X is S, SO, SO2, O, C=O, and CR 2b R 3b Selected from R 2b and R 3b is independently selected from hydrogen, OH, or a halogen; B 1a) CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 4b -CONH-(R 4b is C 1-3 C substituted with a 5- or 6-membered heteroaromatic ring optionally substituted with a substituent selected from alkyl and cyclopropyl 1-6 Alkyl or branched C 3-6 alkyl; or CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 5b -CONH-(R 5b is C 1-3 C substituted with phenyl, optionally substituted with a substituent selected from alkyl, cyclopropyl, and cyclopropyl; 1-6 Alkyl, b) halogen; CN; spiroheterocycles such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; -COOH; -CONR 6b R 7b (R 6b and R 7b are independently H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6b and R 7b may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8b R 9b (R 8b and R 9b , H, C 1-3 alkyl and isopropyl; OH; C optionally substituted with OH 1-3 an optionally alkyl-substituted heterocycle; and R 10b -CONH-(R 10b is C1-3 c) aryl, such as phenyl or naphthyl, optionally substituted with a group selected from halogen, C2-alkynyl, CN, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 11b -CONH-(R 11b is C 1-3 C optionally substituted with a substituent selected from alkyl and cyclopropyl 5-7 cycloalkyl, d) halogen; spiroheterocycles such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; CN; -COOH; -CONR 12b R 13b (R 12b and R 13b are independently H, C 1-3 alkyl, cyclopropyl and isopropyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14b R 15b (R 14b and R 15b are independently H, C 1-3 alkyl and isopropyl; OH; C optionally substituted with OH 1-3 an optionally alkyl-substituted heterocycle; and R 16b -CONH-(R 16b is C 1-3 e) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from C 1-6 Alkyl or branched C 3-6 Alkyl;f) C 2-6 alkynyl, R 50 is a) H, b) OH, c) OC which may be substituted with one or more halogens1-6 Phenyl, CN, OR substituted with one or more groups selected from alkyl, phenyl, OH, and halogen. 17b , N.R. 18b R 19b , and CONH2(R 17b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 20b -CONH-, R 20b is C 1-3 alkyl and cyclopropyl; R 18b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 21b -CONH-, R 21b is C 1-3 alkyl and cyclopropyl; R 19b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 22b -CONH-, R 22b is C 1-3 alkyl and cyclopropyl; d) one or more halogens, CN, OR 23b , N.R. 24b R 25b and branched OC optionally substituted with CONH2 3-6 Alkyl (R 23b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 26b -CONH-, R 26b is C 1-3 alkyl and cyclopropyl; R 24b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 27b-CONH-, R 27b is C 1-3 alkyl and cyclopropyl; R 25b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 28 -CONH-, R 28 is C 1-3 alkyl and cyclopropyl; and e) one or more halogens, CN, OR 29 , N.R. 30 R 31 and cyclic OC optionally substituted with CONH2 3-6 Alkyl (R 29 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 32 -CONH-, R 32 is C 1-3 alkyl and cyclopropyl; R 30 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 33 -CONH-, R 33 is C 1-3 alkyl and cyclopropyl; R 31 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 34 -CONH-, R 34 is C 1-3 alkyl and cyclopropyl; The present invention relates to a D-galactopyranose compound, or a pharma- ceutically acceptable salt or solvate thereof.

[0031] In a further aspect, the present invention provides a D-galactopyranose compound of formula (1): [ka] During the ceremony, The pyranose ring is α-D-galactopyranose, A 1 is R 1 -Z, During the ceremony, Z is a 5-membered heterocycle having at least one heteroatom selected from O, S and N, excluding 1,2,3-triazole, and is linked to α-D-galactopyranose; R 1 a) halogens, CN; -COOH; -CONR 6a R 7a (R 6a and R 7a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6a and R 7a may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F; 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8a R 9a (R 8a and R 9a are independently H, C 1-3 alkyl and isopropyl; OH; and R 10a -CONH-(R 10a is C 1-3 a) aryl, such as phenyl or naphthyl, optionally substituted with a group selected from: alkyl; cyclopropyl; b) halogen; spiroheterocycle; CN; -COOH; -CONR 12a R 13a (R 12a and R 13a are independently H, C 1-3alkyl, cyclopropyl and isopropyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14a R 15a (R 14a and R 15a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl), C(═O)—R 21a (R 21a H and C 1-3 alkyl; OH; and R 16a -CONH-(R 16a is C 1-3 a heterocycle such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl; X is S, SO, SO2, O, C=O, and CR 2b R 3b Selected from R 2b and R 3b is independently selected from hydrogen, OH, or a halogen; B 1 a) CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 4b -CONH-(R 4b is C 1-3 C substituted with a 5- or 6-membered heteroaromatic ring optionally substituted with a substituent selected from alkyl and cyclopropyl 1-6 Alkyl or branched C 3-6 alkyl; or CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 5b -CONH-(R 5b is C 1-3C substituted with phenyl, optionally substituted with a substituent selected from alkyl, cyclopropyl, and cyclopropyl; 1-6 Alkyl, b) halogen; CN; C2-alkynyl; -COOH; -CONR 6b R 7b (R 6b and R 7b are independently H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6b and R 7b may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8b R 9b (R 8b and R 9b , H, C 1-3 alkyl and isopropyl; OH; and R 10b -CONH-(R 10b is C 1-3 c) aryl, such as phenyl or naphthyl, optionally substituted with a group selected from halogen, C2-alkynyl, CN, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 11b -CONH-(R 11b is C 1-3 C optionally substituted with a substituent selected from alkyl and cyclopropyl 5-7 cycloalkyl, d) halogen; spiroheterocycles such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; CN; -COOH; -CONR 12b R 13b (R 12b and R 13b are independently H, C 1-3alkyl, cyclopropyl and isopropyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14b R 15b (R 14b and R 15b are independently H, C 1-3 alkyl and isopropyl; OH; and R 16b -CONH-(R 16b is C 1-3 e) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from C 1-6 Alkyl or branched C 3-6 Alkyl;f) C 2-6 alkynyl, R 50 is a) H, b) OH, c) OC which may be substituted with one or more halogens 1-6 Phenyl, CN, OR substituted with one or more groups selected from alkyl, phenyl, OH, and halogen. 17b , N.R. 18b R 19b , and CONH2(R 17b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 20b -CONH-, R 20b is C 1-3 alkyl and cyclopropyl; R 18b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 21b -CONH-, R 21b is C 1-3 alkyl and cyclopropyl; R19b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 22b -CONH-, R 22b is C 1-3 alkyl and cyclopropyl; d) one or more halogens, CN, OR 23b , N.R. 24b R 25b and branched OC optionally substituted with CONH2 3-6 Alkyl (R 23b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 26b -CONH-, R 26b is C 1-3 alkyl and cyclopropyl; R 24b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 27b -CONH-, R 27b is C 1-3 alkyl and cyclopropyl; R 25b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 28 -CONH-, R 28 is C 1-3 alkyl and cyclopropyl; and e) one or more halogens, CN, OR 29 , N.R. 30 R 31 and cyclic OC optionally substituted with CONH2 3-6 Alkyl (R 29 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 32 -CONH-, R32 is C 1-3 alkyl and cyclopropyl; R 30 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 33 -CONH-, R 33 is C 1-3 alkyl and cyclopropyl; R 31 is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 34 -CONH-, R 34 is C 1-3 alkyl and cyclopropyl; The present invention relates to a D-galactopyranose compound, or a pharma- ceutically acceptable salt or solvate thereof.

[0032] In one embodiment, Z is 1,2,4-triazolyl, oxazolyl, oxadiazolyl, isoxazolyl, dioxolyl, dithiolyl, thiazolyl, isothiazolyl, furanyl, thiophene, pyrrolyl, imidazolyl or [ka] In another embodiment, Z is selected from pyrazolyl such as, for example, wherein the asterisk on the carbon is attached to R1 and the asterisk on the nitrogen is attached to the α-D-galactopyranose. In another embodiment, Z is oxadiazolyl.

[0033] In a further embodiment, R 1 is phenyl optionally substituted with a group selected from CN, OH, NH2, F, Br, Cl, I, methyl optionally substituted with fluorine (F), OCH3 optionally substituted with F, and SCH3 optionally substituted with F.

[0034] In a further embodiment, R 1is phenyl substituted with a group selected from F, Cl and methyl. Typically, R 1 is phenyl substituted with 1, 2 or 3, such as 2 or 3, selected from F, Cl and methyl.

[0035] In yet a further embodiment, R 1 is Br;F;Cl;I;OH;CN;NR 14a R 15a (R 14a and R 15a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl), C(═O)—R 21a (R 21a H and C 1-3 alkyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; OC optionally substituted with F 1-3 alkyl; and SC optionally substituted with F 1-3 Preferably, R is selected from the group consisting of 5- or 6-membered heteroaromatic rings, optionally substituted with a group selected from alkyl. 1 is pyridinyl optionally substituted with a group selected from OH, NH2, CN, Br, Cl, I, F, methyl optionally substituted with F, OCH3 optionally substituted with F, and SCH3 optionally substituted with F, or is pyrimidyl optionally substituted with a group selected from H, CN, Br, Cl, I, F, methyl optionally substituted with F, OCH3 optionally substituted with F, and SCH3 optionally substituted with F.

[0036] In a further embodiment, R 1 is oxazolyl, for example oxazol-2-yl.

[0037] In a further embodiment, R 1 is imidazolyl.

[0038] In a further embodiment, R 1 is pyrazolyl.

[0039] In a further embodiment, R 1 is a 5- or 6-membered heteroaromatic ring selected from the group consisting of formulas 2-9, where the asterisk * indicates the carbon atom of the heteroaromatic ring that is covalently bonded to the Z substituent; [ka] R 2 ~R 23 and R 27 are independently H; halogen; OH; CN; SH; SC 1-3 Alkyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl;NR 24 R 25 (R 24 is H and C 1-3 alkyl; R 25 is H, C 1-3 Alkyl and COR 26 Selected from R 26 is H and C 1-3 alkyl). Preferably, R 1 teeth, [ka] is selected from the group consisting of R 2 is selected from the group consisting of OH, methyl and halogen, preferably F, Cl and Br; R 3 is hydrogen, C 1-6 selected from the group consisting of alkyl and halogen; R 4is selected from the group consisting of OH, NH2 and halogens, preferably F, Cl and Br, R 5 is hydrogen, C 1-6 It is selected from the group consisting of alkyl and halogen.

[0040] In still further embodiments, X is selected from S, SO, SO2, and O, such as S, SO, and SO2, preferably S.

[0041] In a further embodiment, B1 is selected from heteroaryl, optionally substituted with a group selected from halogen, CN, and methyl, optionally substituted with F. Preferably, B1 is selected from pyridinyl, optionally substituted with a group selected from Cl, Br, CN; methyl; CF3; pyridine; pyrimidine; oxazole; and thiazole.

[0042] In further embodiments, B1 is selected from the group consisting of halogen; CN; ethynyl; methyl optionally substituted with F; and C optionally substituted with OH. 1-3 Heteroaryl optionally substituted with a group selected from heterocycles optionally substituted with alkyl. Preferably, B1 is selected from Cl, Br, CN, methyl, CF3, azetidinyl, azetidinyl substituted with CH2OH, pyridinyl, pyrimidinyl, oxazolyl and pyridinyl optionally substituted with a group selected from thiazolyl.

[0043] In a further embodiment, B1 is a C substituted or unsubstituted halogen or C substituted or unsubstituted C 1-3 phenyl optionally substituted with a group selected from alkyl.

[0044] In a further embodiment, B1 is a C1 optionally substituted with halogen, CN, and F. 1-3Typically, B1 is selected from phenyl substituted with one, two or three, for example one or two, selected from Cl, F, Br, CN, methyl and CF3.

[0045] In a further embodiment, B1 is a C1 optionally substituted with halogen, CN, F. 1-3 Alkyl, and CONR 6b R 7b (R 6b and R 7b are independently H, C 1-3 alkyl, cyclopropyl, and isopropyl; or R 6b and R 7b is selected from phenyl optionally substituted with a group selected from (which together with the nitrogen may form a heterocycloalkyl).

[0046] In a further embodiment, R 50 is H; C such as methyl, ethyl or isopropyl 1-4 C substituted with at least one of the following groups: alkyl; phenyl and phenyl substituted with one or more groups selected from OH and halogen; 1-4 In an exemplary embodiment, R 50 is selected from OH.

[0047] In a further embodiment, R 50 OC such as methoxy 1-6 It is an alkyl.

[0048] In a further embodiment, the compound of formula (1) is 3-Chlorophenyl 3-deoxy-3-[4-(3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, and 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,5-difluoro-4-methylphenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside; or a pharma-ceutically acceptable salt or solvate thereof is selected from one of the following:

[0049] In a further embodiment, the compound of formula (1) is 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(6-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(5-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(4-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(1-methyl-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-imidazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(oxazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-Chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside; or a pharma-ceutically acceptable salt or solvate thereof is selected from one of the following:

[0050] In yet a further embodiment, the compound of formula (1) is 3-Chlorophenyl 3-deoxy-3-[4-(3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,5-difluoro-4-methylphenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(6-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(5-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(4-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(1-methyl-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-imidazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(oxazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,3-imidazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-[3,3-bis(hydroxymethyl)azetidin-1-yl]pyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[3-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, and 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside; or a pharmaceutical salt or solvate thereof is selected from one of the following:

[0051] In a further aspect, the present invention relates to a compound of formula (1) for use as a medicament.

[0052] In a still further aspect, the present invention relates to a pharmaceutical composition comprising a compound according to any one of the preceding claims, and optionally pharma- ceutically acceptable excipients such as carriers and / or excipients.

[0053] In a further aspect, the present invention relates to a compound of formula (1) of the present invention for use in a method for treating a disorder associated with the binding of galectins, such as galectin-1 and / or galectin-3, to their ligands in a mammal, such as a human. In a further embodiment, the disorder is inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndromes; fibrosis, such as pulmonary fibrosis, hepatic fibrosis, renal fibrosis, ophthalmological fibrosis and fibrosis of the skin and heart; focal fibrosis such as Dupuytren's disease, Peyronie's disease; fibrotic complications of other treatments such as coronary artery stents, biliary stents, cerebral artery stents, ureteral stents; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonitis. , abnormal scar formation; surgical adhesions; septic shock; cancer, e.g., colorectal cancer, other gastrointestinal cancers, e.g., pancreatic cancer, gastric cancer, biliary tract cancer, lung cancer, mesothelioma, female cancers, e.g., breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube cancer, brain cancers, e.g., medulloblastoma, glioma, meningioma, sarcoma of bone and muscle and other sarcomas, leukemia and lymphomas, e.g., T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven bone diseases such as osteogenesis imperfecta; pulmonary hypertension; psoriasis. , autoimmune diseases such as rheumatoid arthritis, rheumatoid lung; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections such as influenza virus, HIV, herpes virus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or diseases or conditions associated with ocular angiogenesis, such as angiogenesis associated with cancer; and ocular diseases, such as age-related macular degeneration and corneal angiogenesis; atherosclerosis; metabolic diseases; diabetes; type I diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Loeys-Dietz syndrome; nephropathy; diastolic HF; fibrotic pulmonary complications of aPD1 and other CPI therapy; asthma and other interstitial lung diseases, such as Hermansky-Pudlak syndrome, liver disorders, such as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease; uterine diseases, such as uterine fibroids and uterine or cervical fibrosis.

[0054] In yet a further aspect, the present invention relates to a method for the treatment of a disorder associated with the binding of a galectin, such as galectin-1 and / or galectin-3, to its ligand in a mammal, such as a human, wherein a therapeutically effective amount of at least one compound of formula (1) of the present invention is administered to a mammal in need of such treatment. In a further embodiment, the disorder is Inflammation; Inflammation-induced thrombosis; Atopic dermatitis; Acute coronary syndromes; Fibrosis, e.g. pulmonary fibrosis, hepatic fibrosis, renal fibrosis, ophthalmological fibrosis and cutaneous and cardiac fibrosis; Localized fibrosis such as Dupuytren's disease, Peyronie's disease; Fibrotic complications of other treatments such as coronary artery stents, biliary stents, cerebral artery stents, ureteral stents; Scleroderma; Scarring; Keloid formation; COVID-19; Acute lung injury; ARDS; Viral pneumonitis, abnormal scar formation; Surgery adhesions; septic shock; cancer, e.g. colorectal cancer, other gastrointestinal cancers, e.g. pancreatic cancer, gastric cancer, biliary tract cancer, lung cancer, mesothelioma, female cancers, e.g. breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube cancer, brain cancers, e.g. medulloblastoma, glioma, meningioma, bone and muscle sarcoma and other sarcomas, leukemia and lymphomas, e.g. T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven bone diseases such as osteogenesis imperfecta; pulmonary hypertension; psoriasis, autoimmune diseases such as rheumatoid arthritis, rheumatoid lung; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections such as influenza virus, HIV, herpes virus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, e.g. ocular angiogenesis or diseases or conditions associated with ocular angiogenesis, e.g. angiogenesis associated with cancer; and ocular diseases, e.g. age-related macular degeneration and corneal angiogenesis; atherosclerosis; metabolic diseases; diabetes; type I diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Loeys-Dietz syndrome; nephropathy; diastolic HF; fibrotic pulmonary complications of aPD1 and other CPI therapy; asthma and other interstitial lung diseases, e.g. Hermansky-Pudlak syndrome, liver disorders, e.g. non-alcoholic steatohepatitis or non-alcoholic fatty liver disease; uterine diseases such as uterine fibroids and uterine or cervical fibrosis. is selected from the group consisting of:

[0055] Another aspect of the present invention relates to a combination therapy comprising administering a compound of formula (I) of the present invention together with a therapeutically active compound different from the compound of formula (I) (interchangeably referred to as a "different therapeutically active compound"). In one embodiment, the present invention relates to a combination of a compound of formula (I) with a different therapeutically active compound for use in the treatment of a disorder associated with the binding of galectin-1 and / or galectin-3 to its ligand in a mammal. Such disorders are disclosed below.

[0056] In one embodiment of the present invention, a therapeutically effective amount of at least one compound of formula (I) of the present invention is administered to a mammal in need thereof in combination with a different therapeutically active compound. In a further embodiment, the combination of the compound of formula (I) with a different therapeutically active compound is administered to a mammal in need thereof in combination with a different therapeutically active compound for the treatment of inflammation; fibrosis, such as pulmonary fibrosis, hepatic fibrosis, renal fibrosis, ophthalmic fibrosis and dermal and cardiac fibrosis; scarring; keloid formation; abnormal scar formation; surgical adhesions; septic shock; cancer, 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, systemic lupus erythematosus; metabolic disorders; heart disease; heart failure; pathological blood The therapeutic agent is administered to a mammal suffering from a disorder selected from the group consisting of angiogenesis, e.g., ocular angiogenesis or a disease or condition associated with ocular angiogenesis, e.g., angiogenesis associated with cancer; ocular diseases, e.g., age-related macular degeneration and corneal angiogenesis; atherosclerosis; metabolic diseases, e.g., diabetes; type 2 diabetes; insulin resistance; obesity; diastolic HF; asthma and other interstitial lung diseases, e.g., Hermansky-Pudlak syndrome, mesothelioma; and liver diseases, e.g., nonalcoholic steatohepatitis or nonalcoholic fatty liver disease.

[0057] Non-limiting groups of cancers that may be mentioned as examples of cancers that may be treated, managed and / or prevented by administering a compound of formula (I) in combination with a different therapeutically active compound are colon cancer, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, chordoma, angiosarcoma, endothelioma, lymphangiosarcoma, lymphangioendothelioma, synovium, mesothelioma, Ewing's sarcoma, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, cholangiocarcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung cancer, small cell lung cancer, bladder cancer, Epithelial cancer, glioblastoma, schwannoma, craniopharingiomas, neurofibromas, gliomas, astrocytomas, medulloblastomas, craniopharyngiomas, ependymoma, pineal tumors, hemangioblastomas, acoustic neurinomas, oligodendroglioma, meningiomas, melanomas, neuroblastomas, retinoblastomas, leukemias and lymphomas, acute lymphocytic leukemia and acute myeloid polycythemia vera, multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain disease, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, rectal cancer, urological cancer, uterine cancer, oral cancer, skin cancer, stomach cancer cancer), brain tumor, liver cancer, laryngeal cancer, esophageal cancer, breast cancer, childhood acute lymphoblastic leukemia (ALL), thymic ALL, B-cell ALL, acute myeloid leukemia, myelomonocytic leukemia, acute megakaryocytic leukemia, Burkitt's lymphoma, acute myeloid leukemia, chronic myeloid leukemia, and T-cell leukemia, small cell lung cancer and large cell non-small cell lung cancer, acute granulocytic leukemia, germ cell tumor, endometrial cancer, gastric cancer, head and neck cancer, chronic lymphocytic leukemia, hairy cell leukemia, and thyroid cancer.

[0058] In some embodiments of the present invention, administration of at least one compound of formula (I) of the present invention and at least one additional therapeutic agent exhibits therapeutic synergy.In some embodiments of the method of the present invention, the measured response to treatment observed after administration of both at least one compound of formula (I) of the present invention and an additional therapeutic agent is improved compared to the same measured response to treatment observed after administration of either at least one compound of formula (I) of the present invention or an additional therapeutic agent alone.

[0059] A further aspect of the present invention relates to a combination therapy comprising administering a compound of formula (I) of the present invention together with an antifibrotic compound in a form different from that of the compound of formula (I) to a mammal in need thereof. In a further embodiment, such an antifibrotic compound may be selected from the non-limiting group of 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.

[0060] A further aspect of the invention relates to combination therapy comprising administering a compound of formula (I) to a mammal in need thereof in combination with a further conventional cancer treatment, such as chemotherapy or radiation therapy, or with immunostimulant therapy, gene therapy, antibody therapy, and dendritic cell therapy, or with mRNA-based therapy, including mRNA-based cancer vaccines and / or viral-based cancer vaccines.

[0061] In one embodiment, the compound of formula (I) is administered with at least one additional therapeutic agent selected from anti-neoplastic chemotherapeutic agents. In further embodiments, the anti-neoplastic chemotherapeutic agent is selected from all-trans retinoic acid, actimid, azacitidine, azathioprine, bleomycin, carboplatin, capecitabine, cisplatin, chlorambucil, cyclophosphamide, cytarabine, daunorubicin, docetaxel, doxifluridine, doxorubicin, epirubicin, etoposide, fludarabine, fluorouracil, gemcitabine, hydroxyurea, idarubicin, irinotecan, lenalidomide, leucovorin, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, revlimid, temozolomide, teniposide, thioguanine, valrubicin, vinblastine, vincristine, vindesine, and vinorelbine. In one embodiment, the chemotherapy agent for use in the combination of this agent can be a combination of different chemotherapy agents.Suitable combinations include FOLFOX and IFL.FOLFOX is a combination that includes 5-fluorouracil (5-FU), leucovorin, and oxaliplatin.IFL treatment includes irinotecan, 5-FU, and leucovorin.

[0062] In further embodiments of the invention, the additional conventional cancer treatment comprises radiation therapy. In some embodiments, the radiation therapy comprises localized radiation therapy delivered to the tumor. In some embodiments, the radiation therapy comprises total body irradiation.

[0063] In another embodiment of the present invention, the additional cancer treatment is selected from the group of immune stimulants, such as, for example, cytokines and antibodies. Such cytokines may be selected from the group consisting of, but are not limited to, GM-CSF, type I IFN, interleukin 21, interleukin 2, interleukin 12 and interleukin 15. The antibody is preferably an immune stimulant antibody, such as anti-CD40 antibody or anti-CTLA-4 antibody. The immune stimulant may be a substance capable of depleting immune suppressive cells (e.g., regulatory T cells) or factors, which may be, for example, an E3 ubiquitin ligase. E3 ubiquitin ligases (HECT, RING and U-box proteins) have emerged as important molecular regulators of immune cell function, and each may be involved in regulating immune responses during infection by targeting specific inhibitory molecules for proteolytic destruction. Several HECT and RING E3 proteins are also involved in the induction and maintenance of immune self-tolerance, and c-Cbl, Cbl-b, GRAIL, Itch and Nedd4 negatively regulate T cell growth factor production and proliferation, respectively.

[0064] In some embodiments of the present invention, the compound of formula (I) is administered with at least one additional therapeutic agent selected from checkpoint inhibitors.In some embodiments of the present invention, the checkpoint inhibitors act on one or more of the following non-limiting targets: CEACAM1, Galectin-9, TIM3, CD80, CTLA4, PD-1, PD-L1, HVEM, BTLA, CD160, VISTA, B7-H4, B7-2, CD155, CD226, TIGIT, CD96, LAG3, GITF, OX40, CD137, CD40, IDO and TDO, kynurenine antagonists.These are known targets, and some of these targets are described in Melero et al.Nature Reviews Cancer (2015). Examples of checkpoint inhibitors administered with the compounds of formula (1) are anti-PD-1: nivolumab, pembrolizumab, cemiplimab, anti-PD-L 1: atezolizumab, avelumab, durvalumab and one anti-CTLA-4: ipilimumab. Each of these checkpoint inhibitors can be the subject of an embodiment in combination with any one of the compounds of formula (1).

[0065] In some embodiments of the invention, the compound of formula (I) is administered with at least one additional therapeutic agent selected from inhibitors of indoleamine-2,3-dioxygenase (IDO).

[0066] In some embodiments of the present invention, the compound of formula (I) is administered with at least one additional therapeutic agent selected from one or more inhibitors of the CTLA4 pathway. In some embodiments, the inhibitors of the CTLA4 pathway are selected from one or more antibodies against CTLA4.

[0067] In some embodiments of the invention, the compound of formula (I) is administered with at least one additional therapeutic agent selected from one or more inhibitors of the PD-1 / PD-L pathway. In some aspects, the one or more inhibitors of the PD-1 / PD-L pathway are selected from one or more antibodies or antibody fragments against PD-1, PD-L 1, and / or PD-L 2, or other methods by which anti-PD 1 antibodies can be induced, such as mRNA-based introduction of genetic material directing the endogenous production of anti-PD 1 or anti-PDL 1 antibodies or fragments of such antibodies.

[0068] In yet a further aspect, the present invention provides a compound comprising R 1 , X, B 1 , L 1 and Z is defined as above under formula 1, comprising step a1: [ka] a1)L 1 is defined as bromine or iodine [ka] Compounds of formula I, L, etc. 1 -Z is reacted with R in the presence of a metal organocatalyst such as Pd(dppf)Cl2 and a base such as potassium carbonate in a solvent such as dioxane and optionally water at elevated temperature. 1 -B(OH)2 or 4,4,5,5-tetramethyl-1,3,2-dioxaborolane-R 1 With a boronic acid or borinate of the formula, etc., to provide a compound of formula II.

[0069] In a further aspect, the present invention relates to a method for the preparation of a compound comprising the steps of: 1 The present invention relates to a process for the preparation of a compound of formula II or a pharma- ceutically acceptable salt or solvate thereof, comprising steps a2 to a7, wherein, Z, X are as defined above in formula 1: [ka] a2) reacting a compound of formula III with a reagent such as trifluoromethanesulfonic anhydride to give L 2 is a leaving group such as triflate to give a compound of formula IV. a3) reacting a compound of formula IV with L 1 is defined as a halide such as bromine or iodine [ka] Equation L such as 1 -Z to give a compound of formula V. a4) The compound of formula V is reacted with TFA and water, with removal of water by azeotropic distillation, to give a product which is further reacted with acetic anhydride, an organic base, e.g. triethylamine TEA, in a solvent such as ethanol to give a compound of formula VI. a5) Reacting a compound of formula VI with a reagent such as dichloromethyl methyl ether or PCl5 in the presence of a Lewis acid such as BF3Et2O in an inert solvent such as dichloromethane or chloroform to give L 3 is defined as a halogen, such as chlorine, to obtain a compound of formula VII. a6) reacting a compound of formula VII with B in the presence of a base such as sodium hydride in an inert solvent such as DMF 1 - B such as SH 1 Reaction with a reagent such as --XH provides a compound of formula VIII. a7) Reacting a compound of formula VIII with a base such as sodium methoxide in a solvent such as methanol to give a compound of formula I.

[0070] In yet a further aspect, the present invention provides a method for producing a composition comprising the steps of: 1 ,B 1 and step a8, wherein X is as defined above in formula 1: [ka] a8)Y 1-3 A compound of formula IX, where Y is defined as the acetate salt, is reacted with a base such as sodium methoxide in a solvent such as methanol to give Y 7 is hydrogen, and optionally 1 and Y 2 together form a benzylidene, and a compound of formula IX, where Y is an alkyl, such as methyl, is reacted with an acid, such as TFA, to form a benzylidene. 7 is an alkyl group such as methyl to give a compound of formula XVIII.

[0071] In yet a further aspect, the present invention provides a method for producing a composition comprising the steps of: 1 ,B 1 and steps a9 to a11, wherein X is as defined above in formula 1, for preparing a compound of formula XII or a pharma- ceutically acceptable salt or solvate thereof. 1 is defined as bromine or iodine. [ka] a9) [ka] L such as 1 Compound VI, where R is -Z, is reacted with R in the presence of a metal organic catalyst, such as Pd(dppf)Cl, and a base, such as potassium carbonate, in a solvent, such as dioxane and optionally hot water. 1 -B(OH)2 or 4,4,5,5-tetramethyl-1,3,2-dioxaborolane-R 1 to give a compound of formula X. a10) reacting a compound of formula X with a reagent such as dichloromethyl methyl ether or PCl5 in the presence of a Lewis acid such as BF3Et2O in an inert solvent such as dichloromethane or chloroform to give L 4 is defined as a halogen, such as chlorine, to give a compound of formula XI. a11) Compound of formula XI is reacted with B in the presence of a base such as sodium hydride in an inert solvent such as DMF. 1 - B such as SH 1 Reaction with a reagent such as -XH provides a compound of formula XII.

[0072] In yet a further aspect, the present invention provides a method for producing a composition comprising the steps of: 1 ,B 1 and steps a12-a13, wherein X is as defined above in formula 1, for preparing a compound of formula XII or a pharma- ceutically acceptable salt or solvate thereof. 1 is defined as bromine or iodine. [ka] a12) [ka] L such as 1 The compound of formula VIII in -Z is reacted with bis(pinacolato)diboron in the presence of a metallo-organic reagent such as Pd(dppf)Cl2 and a base such as potassium acetate in a solvent such as DMSO to give the compound of formula XIII. a13) reacting a compound of formula XIII with L in the presence of a base such as Na2CO3, in a solvent such as toluene, in the presence of a metallo-organic reagent such as tetrakis(triphenylphosphine)palladium 5 is a halide such as Cl, Br or I 1 -L 5 to give a compound of formula XII. 1 is defined as bromine or iodine.

[0073] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 and steps a14 to a16, wherein X is as defined above in formula 1, for preparing a compound of formula XIII or a pharma- ceutically acceptable salt or solvate thereof. 1 is defined as bromine or iodine. [ka] a14)L 1 -Z [ka] A compound of formula VI, defined as: is reacted with bis(pinacolato)diboron in the presence of a metallo-organic reagent, such as Pd(dppf)Cl2, and a base, such as potassium acetate, in a solvent, such as DMF, to provide a compound of formula XIV. a15) Reacting a compound of formula XIV with a reagent such as dichloromethyl methyl ether or PCl5 in the presence of a Lewis acid such as BF3Et2O in an inert solvent such as dichloromethane or chloroform to give L 6 is defined as a halogen, such as chlorine, to obtain a compound of formula XV. a16) Compound XV is reacted with B in the presence of a base such as sodium hydride in an inert solvent such as DMF. 1 - B such as SH 1 Reaction with a reagent such as -XH provides a compound of formula XIII.

[0074] In yet a further aspect, the present invention provides a method for producing a composition comprising the steps of: 1 ,B 1 and steps a17-a18, wherein X is as defined above in formula 1, for preparing a compound of formula XIII or a pharma- ceutically acceptable salt or solvate thereof. 1 is defined as bromine or iodine. [ka] a17) Reacting a compound of formula II with benzaldehyde dimethyl acetal and methanesulfonic acid to give Y 5 and Y 5 together to form a protecting group such as benzylidene to give a compound of formula XVI. a18)Y 5 and Y 5A compound of formula XVI, in which Y and Y together form a protecting group such as benzylidene, is reacted with an alkyl halide such as iodomethane in the presence of a base such as sodium hydride in a solvent such as DMF to give Y. 5 and Y 5 together form a protecting group such as benzylidene, and Y 6 is methyl to obtain a compound of formula XVII.

[0075] In yet a further aspect, the present invention provides a compound comprising R 1 , X and B 1 The method for preparing a compound of formula XXI or a pharma- ceutically acceptable salt or solvate thereof comprises steps a19-a20, wherein the compound is as defined above in formula 1: [ka] a19) Reaction of a compound of formula XVIII with sodium methoxide in methanol gives a product which is further reacted with 1,3-propanedithiol and an organic base such as triethylamine in a solvent such as methanol to give a compound of formula XIX. a20) formula [ka] This compound is reacted with phosphorus(V) oxyl chloride in a solvent such as dimethoxyethane, followed by the addition of triethylamine to give the intermediate product A. The compound of formula XIX is reacted with oxoacetic acid and a base such as potassium carbonate in DMF, followed by reaction with product A to give the compound of formula XXI.

[0076] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 The present invention relates to a process for preparing a compound of formula XXIV or a pharma- ceutically acceptable salt or solvate thereof, comprising steps a21 to a23, wherein L, Z and X are as defined above in formula 1. 1 is defined as bromine or iodine.

[0077] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 The present invention relates to a process for preparing a compound of formula XIII or a pharma- ceutically acceptable salt or solvate thereof, comprising steps a21 to a23, wherein X and Z are as defined above in formula 1. 1 is defined as bromine or iodine, and Y 7 and Y 8 together form a protecting group such as benzylidene, and Y 9 is an alkyl group such as methyl. [ka] a21) The compound of formula I is reacted with benzaldehyde dimethyl acetal and methanesulfonic acid to give the compound of formula XXII. a22) A compound of formula XXII is reacted with an alkyl halide, such as iodomethane, in the presence of a base, such as sodium hydride, in an inert solvent, such as DMF, to give a compound of formula XXIII. a23) Reacting a compound of formula XXIII with an acid such as TFA to give a compound of formula XXIV.

[0078] In yet a further aspect, the present invention provides a compound comprising R 1 and B. 1 The method for preparing a compound of formula XXXIII or a pharma- ceutically acceptable salt or solvate thereof comprises steps a24 to a31, wherein [ka] a24) Reaction of a compound of formula XXV with dibutyltin oxide in a solvent such as dry methanol at elevated temperature, followed by reaction with allyl bromide in the presence of tetrabutylammonium bromide in a solvent such as toluene, gives a compound of formula XXVI. a25) Reaction of a compound of formula XXVI with benzyl bromide in the presence of a base such as sodium hydride in a solvent such as DMF to give an intermediate compound which is further reacted with palladium(II) chloride in a solvent such as methanol to give another intermediate product which is further reacted with Dess-Martin peroxinan in a solvent such as dichloromethane to give a compound of formula XXVII. a26) Reaction of a compound of formula XXVII with a cyanating reagent, such as trimethylsilyl cyanide, in the presence of AlCl 3 in a solvent, such as DCM, gives a compound of formula XXVIII. a27) The compound of formula XXVIII is reacted with O-phenylchloromethanethioate in the presence of an organic base 4-(dimethylamino)pyridine and triethylamine in a solvent such as acetonitrile to give a compound which is further reacted with 2,2'-azobis(2-methylpropionitrile and tris(trimethylsilyl)silane in a solvent such as toluene to give a compound of formula XXIX. a28) A compound of formula XXIX is reacted with hydrogen peroxide in the presence of potassium carbonate in a solvent such as DMSO to give a compound of formula XXX. a29) reacting a compound of formula XXX with a compound of formula [ka] to give a compound of formula XXXI. A30) A compound of formula XXXI is reacted with hydrogen gas in the presence of Pd / C in a solvent such as methanol to give an intermediate compound which is further reacted with acetic anhydride in the presence of a base such as pyridine to give an intermediate compound which is further reacted with acetic anhydride in the presence of acetic acid and sulfuric acid to give a compound of formula XXXII. a31) reacting a compound of formula XXXII with a compound of formula R in the presence of boron trifluoride diethyl etherate in 1,2-dichloroethane 1 -SH compound to give the compound of formula XXXIII.

[0079] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 and B. 1 The present invention relates to a process for the preparation of a compound of formula XXXVII or a pharma- ceutically acceptable salt or solvate thereof, comprising steps a32-a35 as defined above in formula 1. [ka] a32) A compound of formula XXX is reacted with Lawesson's reagent in THF to give a compound of formula XXXIV. a29) reacting a compound of formula XXXIV with a compound of formula [ka] to give a compound of formula XXXV. A30) A compound of formula XXXV is reacted with trichloroborane in a solvent such as DCM to give an intermediate compound which is further reacted with acetic anhydride in the presence of a base such as pyridine to give an intermediate compound which is further reacted with acetic anhydride in the presence of acetic acid and sulfuric acid to give a compound of formula XXXVI. a31) reacting a compound of formula XXXVI with a compound of formula R in the presence of boron trifluoride diethyl etherate in 1,2-dichloroethane 1 -SH compound to give the compound of formula XXXVII.

[0080] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 and B. 1 The present invention relates to a process for the preparation of a compound of formula XLII or a pharma- ceutically acceptable salt or solvate thereof, comprising steps a36 to a40 as defined above in formula 1: [ka] a36) Reaction of a compound of formula XXX with HCl followed by sodium nitrite in a solvent such as dioxane gives a compound of formula XXXVIII. a37) Compounds of formula XXXVIII and formula R 1A compound of -C(O)NHNH2 is reacted with a reagent such as HATU in the presence of an organic base such as triethylamine to give a compound of formula XXXIX. a38) A compound of formula XXXIX is reacted with Burgess reagent in a solvent mixture such as DMF / THF at elevated temperature to give a compound of formula XL. a39) A compound of formula XL is reacted with hydrogen in the presence of Pd / C in a solvent such as methanol to give an intermediate compound which is further reacted with acetic anhydride in the presence of a base such as pyridine to give an intermediate compound which is further reacted with acetic anhydride in the presence of acetic acid and sulfuric acid to give a compound of formula XLI. a40) reacting a compound of formula XLI with a compound of formula R in the presence of boron trifluoride diethyl etherate in 1,2-dichloroethane 1 -SH compound to give the compound of formula XLII.

[0081] In yet a further aspect, the present invention provides a method for the preparation of a medicament for the treatment of cancer, comprising: 1 which relates to a process for the preparation of a compound of formula XLIV comprising step a41, which is defined as above in formula (1): [ka] a41) A compound of formula XLIII is reacted with Na2S·10H2O in the presence of a base such as NaOH in an inert solvent such as DMF to give a compound of formula XLIV.

[0082] In any process step, B 1 It is understood that a42 to a45 below can be carried out as part of other processes described above in which is defined as a substituent of an intermediate or product.

[0083] In yet a further aspect, the present invention provides a method for the preparation of a medicament for the treatment of cancer, comprising: 1 The process for preparing a compound of formula XLVI comprises a step a42, which is defined as above in formula (1): [ka] a42)L4 Compounds of formula XLV, where is a leaving group such as bromine or iodine, are reacted with CuCN or zinc cyanide, optionally in the presence of reagents such as tris(dibenzylideneacetone)dipalladium(0) and 1,1′-bis(diphenylphosphino)ferrocene, at elevated temperature in an inert solvent such as dimethylformamide to provide compounds of formula XLVI.

[0084] In yet a further aspect, the present invention provides a method for the preparation of a medicament for the treatment of cancer, comprising: 1 is defined as above under formula (1), comprising step a43: [ka] a43)L 5 The compound of formula XLVII, where is a leaving group such as bromine or iodine, is reacted with an ethynyl reagent such as trimethylsilylacetylene in the presence of a metallo-organic reagent such as Pd(PPh3)2Cl2 and CuI in a solvent such as THF to give a product which is optionally further reacted with TBAF to give the compound of formula XLVIII.

[0085] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 ,R 6b ,R 7b ,R 12b ,R 13b wherein the formula (1) is defined as above, a process for the preparation of a compound of formula LX, comprising step a44: [ka] a44) A compound of formula XLIX is reacted with a base such as sodium hydroxide to give an intermediate compound which is reacted with HNR in the presence of a coupling reagent such as N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, optionally in the presence of a reagent such as 1-hydroxybenzotriazole hydrate and an organic base such as triethylamine, in a solvent such as DMF. 6b R 7b or HNR 12b R 13band reacting with an amide reagent such as Y 9 R 6b or R 12b , Y 10 R 7b , R 13b This gives a compound of formula LX, which is defined as:

[0086] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 For the process for preparing a compound of formula XLVI, comprising step a45, wherein Y 11 and Y 12 can be taken together with the nitrogen to form N-(2-oxa)-6-azaspiro[3.3]heptanyl, where L6 is a leaving group such as chloro, bromo or iodo. [ka] a45) Compounds of formula LXI are reacted with HNY in the presence of a base such as DIPEA in a solvent such as acetonitrile at elevated temperatures. 11 Y 12 to provide a compound of formula LXII.

[0087] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 The present invention relates to a process for the preparation of a compound of formula LXIV, comprising step a46, which is defined as above in formula (1). [ka] a46) p-Toluenesulfinic acid sodium salt is reacted with concentrated HCl in a solvent mixture of water / tert-butyl methyl ether to give an intermediate product which is further reacted with LXIII in the presence of reagents such as D(+)-10-camphorsulfonic acid and formamide in a solvent mixture such as toluene / MeCN to give a compound of formula LXIV.

[0088] In yet a further aspect, the present invention provides a method for the preparation of a compound comprising the steps of: 1 The present invention relates to a process for the preparation of a compound of formula LXIV, comprising step a47, which is defined as above in formula (1). [ka] a47) A compound of formula LXV is reacted with tert-butyldimethylsilyl trifluoromethanesulfonate in the presence of triethylamine in a solvent such as DCM to give an intermediate product which is further reacted with N-bromosuccinimide in a solvent such as ether to give a compound of formula LXVI. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0089] The compounds of formula (1) of the present invention are different from the compounds of the prior art, in particular 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 never be obvious to a person skilled in the art to expect the same or similar activity of both anomers. Thus, the α and β anomers do not generally have the same activity, which is common knowledge to a person skilled in the art. The compounds of the present invention are novel α-D-galactopyranose compounds that unexpectedly showed very high affinity and specificity for galectin-3, and are considered to be novel potential drug candidates. Some of the novel α-D-galactopyranose compounds have affinity for galectin-1, and some for both galectin-1 and galectin-3, and therefore have a broader disease treatment profile compared to selective galectin-1 inhibitors.

[0090] In a broad aspect, the present invention relates to a D-galactopyranose compound of formula (1): [ka] The pyranose ring is α-D-galactopyranose, with A1, X, R 50 and B1 is as defined above. Preferably, X is S. Typically, Z is pyrazolyl, preferably [ka] and the asterisk on the carbon is R 1 The asterisk on the nitrogen is attached to α-D-galactopyranose, and X is S.

[0091] In another embodiment, Z is selected from the group consisting of imidazole, such as 1,3-imidazol-2-yl; oxazolyl, such as oxazol-2-yl; oxadiazolyl; thiazolyl, such as thiazol-2-yl.

[0092] In a preferred embodiment, R 1 is phenyl optionally substituted with a group selected from CN, OH, NH2, F, Br, Cl, I, methyl optionally substituted with fluorine (F), OCH3 optionally substituted with F, and SCH3 optionally substituted with F. Typically, R 1 is phenyl substituted with 1 to 3 groups selected from F, Br, Cl, I, and methyl.

[0093] In another preferred embodiment, R 1 teeth, [ka] and R 2 is selected from the group consisting of OH, methyl and halogen, such as F, Cl and Br; R 3 is hydrogen, C 1-6 In one embodiment, R 2 is a halogen such as Cl, and R 3 is H.

[0094] In another preferred embodiment, R 1 teeth, [ka] and R 4 is selected from the group consisting of OH, NH2 and halogens, such as F, Cl and Br; R 5 is hydrogen, C 1-6 In one embodiment, R 4 is H or OH, and R 5 is H.

[0095] In a further preferred embodiment, R 1 is imidazolyl. In another preferred embodiment, R 1 In a further preferred embodiment, R 1 is C 1-3 In a preferred embodiment, B1 is pyridinyl substituted with a group selected from Cl, Br, C2-alkynyl, CN, methyl, CF3, pyridine, pyrimidine, oxazole and thiazole.

[0096] In a further embodiment, B1 is pyridinyl substituted with a group selected from Cl, Br, ethynyl, CN, methyl. In yet a further embodiment, B1 is pyridinyl substituted with one or two selected from Cl, Br, ethynyl, CN, and methyl.

[0097] In yet further embodiments, B1 is selected from the group consisting of halogen and C optionally substituted with F. 1-3 and phenyl substituted with a group selected from alkyl.

[0098] In further embodiments, B1 is selected from Cl, CN and CONR 6b R 7b (R 6b and R 7bmay be taken together with the nitrogen to form a heterocycloalkyl. In yet a further embodiment, B1 is phenyl substituted with one or two Cl, CN, and CO-azetidinyl.

[0099] In a further embodiment, R 50 is H, OH; C such as methyl, ethyl or isopropyl 1-4 C substituted with at least one selected from the group consisting of alkyl, phenyl, and phenyl substituted with one or more groups selected from OH and halogen; 1-4 is selected from alkyl.

[0100] In one embodiment, R 50 is OH. In another embodiment, R 50 is methoxy.

[0101] In a further embodiment, the compound of formula (1) is 3-Chlorophenyl 3-deoxy-3-[4-(3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, and 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,5-difluoro-4-methylphenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside is selected from one of the following:

[0102] In yet a further embodiment, the compound of formula (1) is 3-Chlorophenyl 3-deoxy-3-[4-(3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,5-difluoro-4-methylphenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(6-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(5-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(4-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(1-methyl-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-imidazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(oxazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,3-imidazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-[3,3-bis(hydroxymethyl)azetidin-1-yl]pyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[3-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-[5-(4-chlorothiazol-2-yl)-1-methyl-1H-1,2-pyrazol-3-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, and 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside is selected from one of the following:

[0103] In yet a further embodiment, the compound of formula (1) is 3-Chlorophenyl 3-deoxy-3-[4-(3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,5-difluoro-4-methylphenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(6-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(5-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(4-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(1-methyl-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-imidazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(oxazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-Chloropyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,3-imidazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-[3,3-bis(hydroxymethyl)azetidin-1-yl]pyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[3-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, and 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside is selected from one of the following:

[0104] As described in the experimental section, Z is pyrazole, X is S, and R 1 is as defined above, and R 51 R is defined above 50 Some of the prepared compounds of formula 1, wherein B1 is as defined above, have high oral bioavailability and good CNS potential, as evidenced by the data in the experimental section below.

[0105] In one particular embodiment, the present invention provides a compound of formula 1A [ka] During the ceremony, The pyranose ring is α-D-galactopyranose, R 1 a) halogens, CN; -COOH; -CONR 6a R 7a (R 6a and R 7a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6a and R 7a may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F;1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8a R 9a (R 8a and R 9a are independently H, C 1-3 alkyl and isopropyl; OH; and R 10a -CONH-(R 10a is C 1-3 a) aryl, such as phenyl or naphthyl, optionally substituted with a group selected from: alkyl; cyclopropyl; b) halogen; spiroheterocycle; CN; -COOH; -CONR 12a R 13a (R 12a and R 13a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14a R 15a (R 14a and R 15a are independently H, C 1-3 alkyl, cyclopropyl and isopropyl), C(═O)—R 21a (R 21a H and C 1-3 alkyl; OH; and R 16a -CONH-(R 16a is C 1-3 a heterocycle such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl; B 1a) CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 4b -CONH-(R 4b is C 1-3 C substituted with a 5- or 6-membered heteroaromatic ring optionally substituted with a substituent selected from alkyl and cyclopropyl 1-6 Alkyl or branched C 3-6 alkyl; or CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 5b -CONH-(R 5b is C 1-3 C substituted with phenyl, optionally substituted with a substituent selected from alkyl, cyclopropyl, and cyclopropyl; 1-6 Alkyl, b) halogen; CN; C2-alkynyl; -COOH; -CONR 6b R 7b (R 6b and R 7b are independently H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6b and R 7b may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8b R 9b (R 8b and R 9b , H, C 1-3 alkyl and isopropyl; OH; C optionally substituted with OH 1-3 an optionally alkyl-substituted heterocycle; and R 10b -CONH-(R 10b is C 1-3c) aryl, such as phenyl or naphthyl, optionally substituted with a group selected from halogen, C2-alkynyl, CN, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 11b -CONH-(R 11b is C 1-3 C optionally substituted with a substituent selected from alkyl and cyclopropyl 5-7 cycloalkyl, d) halogen; spiroheterocycles such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; CN; -COOH; -CONR 12b R 13b (R 12b and R 13b are independently H, C 1-3 alkyl, cyclopropyl and isopropyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14b R 15b (R 14b and R 15b are independently H, C 1-3 alkyl and isopropyl; OH; C optionally substituted with OH 1-3 an optionally alkyl-substituted heterocycle; and R 16b -CONH-(R 16b is C 1-3 e) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from C 1-6 Alkyl or branched C 3-6 Alkyl;f) C 2-6 alkynyl, R 51 a1) OH, and a2) OC which may be substituted with one or more halogens.1-6 Phenyl, CN, OR substituted with one or more groups selected from alkyl, phenyl, OH, and halogen. 17b , N.R. 18b R 19b , and CONH2(R 17b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 20b -CONH-, R 20b is C 1-3 alkyl and cyclopropyl; R 18b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 21b -CONH-, R 21b is C 1-3 alkyl and cyclopropyl; R 19b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 22b -CONH-, R 22b is C 1-3 alkyl and cyclopropyl; or a pharma- ceutically acceptable salt or solvate thereof.

[0106] In one embodiment of Formula 1A, R 1 is halogen;CN;-COOH;-CONR 6a R 7a (R 6a and R 7a are independent of each other, H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6a and R 7a may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F 1-3Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8a R 9a (R 8a and R 9a are independent of each other, H, C 1-3 alkyl and isopropyl; OH; and R 10a -CONH-(R 10a is C 1-3 In a further embodiment of Formula 1A, R is selected from aryl, such as phenyl or naphthyl, optionally substituted with a group selected from alkyl, cyclopropyl, and cyclopropyl. 1 is selected from phenyl substituted with a group selected from halogen. Typically, R 1 is preferably selected from phenyl substituted with two or three halogens, such as Cl or F, at the meta and / or para positions on the phenyl. The halogens must not be in the ortho positions on the phenyl.

[0107] In one embodiment of Formula 1A, B 1 b) halogen; CN; C2-alkynyl; -COOH; -CONR 6b R 7b (R 6b and R 7b are independent of each other, H, C 1-3 alkyl, cyclopropyl and isopropyl, or R 6b and R 7b may form a heterocycloalkyl together with the nitrogen; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 8b R 9b (R 8b and R 9bare independent of each other, H, C 1-3 alkyl and isopropyl; OH; C optionally substituted with OH 1-3 an optionally alkyl-substituted heterocycle; and R 10b -CONH-(R 10b is C 1-3 aryl, such as phenyl or naphthyl, optionally substituted with a group selected from alkyl and cyclopropyl; and d) halogen; spiroheterocycle, such as N-(2-oxa)-6-azaspiro[3.3]heptanyl; C2-alkynyl; CN; -COOH; -CONR 12b R 13b (R 12b and R 13b are independently H, C 1-3 alkyl, cyclopropyl and isopropyl; C optionally substituted with F 1-3 Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F 1-3 Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR 14b R 15b (R 14b and R 15b are independently H, C 1-3 alkyl and isopropyl; OH; C optionally substituted with OH 1-3 an optionally alkyl-substituted heterocycle; and R 16b -CONH-(R 16b is C 1-3 In a further embodiment of formula 1A, B is selected from the group consisting of heterocycles, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from alkyl and cyclopropyl. 1 is selected from phenyl substituted with one or two substituents selected from halogen and CN, such as Cl and CN. Typically, B 1 is selected from phenyl substituted with two substituents selected from Cl and CN, such as one Cl and one CN. In a further embodiment of formula 1A, B1 is selected from pyridyl substituted with one or two substituents selected from one or more of halogen, CN and ethynyl. Typically, B 1 is selected from pyridyl substituted with one substituent selected from one or more of Br, Cl, CN, and ethynyl. 1 is selected from pyridyl substituted with two substituents selected from one or more of Br, Cl, CN and ethynyl.

[0108] In one embodiment of Formula 1A, R 51 is selected from a1) OH, and a2) phenyl substituted with one or more groups selected from halogen, phenyl, OH, and halogen, CN, OR 17b , N.R. 18b R 19b and CONH2(R 17b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH and R 20b -CONH-(R 20b is C 1-3 alkyl and cyclopropyl; R 18b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 21b -CONH-(R 21b is C 1-3 alkyl and cyclopropyl; R 19b is H, CN, halogen, methyl optionally substituted with F, OCH3 optionally substituted with F, OCH2CH3 optionally substituted with F, OH, and R 22b -CONH-(R 22b is C 1-3 OC optionally substituted with alkyl, cyclopropyl, 1-6 In a further embodiment of Formula 1A, R 51 OH and OC 1-4alkyl. Typically, R 51 is selected from OH and OCH3.

[0109] Those skilled in the art will appreciate that it may be necessary to adjust or change the order of steps a1-a6 of processes, and that such changes in order are encompassed by the process embodiments as described above in the reaction schemes and the accompanying description of the process steps.

[0110] Moreover, those skilled in the art will appreciate that the functional groups of the processes and intermediate compounds described above and below may need to be protected by protecting groups.

[0111] Functional groups which it is desirable to protect include hydroxy, amino and carboxylic acid. Suitable protecting groups for hydroxy include optionally substituted and / or unsaturated alkyl groups (e.g., methyl, allyl, benzyl or tert-butyl), trialkylsilyl or diarylalkylsilyl groups (e.g., t-butyldimethylsilyl, t-butyldiphenylsilyl or trimethylsilyl), AcO (acetoxy), TBS (t-butyldimethylsilyl), TMS (trimethylsilyl), PMB (p-methoxybenzyl) and tetrahydropyranyl. Suitable protecting groups for carboxylic acid include (C 1-6 )-alkyl or benzyl esters. Suitable protecting groups for amino include t-butyloxycarbonyl, benzyloxycarbonyl, 2-(trimethylsilyl)-ethoxy-methyl or 2-trimethylsilylethoxycarbonyl (Teoc). Suitable protecting groups for S include SC(=N)NH2, TIPS.

[0112] Protection and deprotection of functional groups can be carried out before or after any of the reactions in the above-mentioned processes.

[0113] Furthermore, those skilled in the art will appreciate that the individual process steps described above can be performed in a different order and / or individual reactions can be carried out at different stages in the overall pathway (i.e., substituents can be added and / or chemical transformations can be carried out on intermediates other than those mentioned above in connection with a particular reaction) in order to obtain the compounds of the invention in an alternative, and in some cases more convenient, manner, which may negate or require the need for protecting groups.

[0114] In a further embodiment, compound (1) is in free form. As used herein, "in free form" refers to the compound of formula (1) in either acid or base form, depending on the substituents, or as a neutral compound. The free form does not have any additional acid or base salts. In one embodiment, the free form is anhydrous. In another embodiment, the free form is a solvate (e.g., hydrate).

[0115] In a further embodiment, the compound of formula (1) is in crystalline form. Those skilled in the art can carry out tests to find polymorphs, and such polymorphs are intended to be encompassed by the term "crystalline form" as used herein.

[0116] When the compounds and pharmaceutical compositions disclosed herein are used for the above treatments, a therapeutically effective amount of at least one compound is administered to a mammal in need of such treatment.

[0117] As used herein, the term "C 1-x "Alkyl" refers to an alkyl group containing 1-x carbon atoms, e.g., C such as methyl, ethyl, propyl, butyl, pentyl or hexyl. 1-5 or C 1-6 It is.

[0118] The term "C2-alkynyl" as used herein means a -CCH group, where two carbon atoms are joined by a triple bond.

[0119] As used herein, the term "branch C3-6 "Alkyl" means a branched alkyl group containing 3 to 6 carbon atoms, and examples include isopropyl, isobutyl, tert-butyl, isopentyl, 3-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 2,2-dimethylbutyl, and 2,3-dimethylbutyl.

[0120] As used herein, the term "C 3-7 "Cycloalkyl" means a cyclic alkyl group containing from 3 to 7 carbon atoms and includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and 1-methylcyclopropyl.

[0121] As used herein, the term "C 5-7 "Cycloalkyl" means a cyclic alkyl group containing from 5 to 7 carbon atoms, for example, cyclopentyl, cyclohexyl, or cycloheptyl.

[0122] The term "oxo" as used herein means an oxygen atom having a double bond, also depicted as O=.

[0123] As used herein, the term "CN" means nitrile.

[0124] The term "5- or 6-membered heteroaromatic ring" as used herein means one 5-membered heteroaromatic ring or one 6-membered heteroaromatic ring. A 5-membered heteroaromatic ring contains 5 ring atoms, of which 1-4 are heteroatoms selected from N, O and S. A 6-membered heteroaromatic ring contains 6 ring atoms, of which 1-5 are heteroatoms selected from N, O and S. Examples include thiophene, furan, pyran, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine and pyridazine. When such heteroaromatic rings are substituents, they are referred to as thiophenyl, furanyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, pyridinyl, pyrazinyl, pyrimidinyl and pyridazinyl. Also included are oxazoyl, thiazoyl, thiadiazoyl, oxadiazoyl and pyridonyl.

[0125] The term "heterocycle, such as heteroaryl or heterocycloalkyl," as used herein, refers to a heterocycle consisting of one or more 3- to 7-membered ring systems containing one or more heteroatoms, which may optionally be aromatic. The term "heteroaryl," as used herein, refers to a monocyclic or bicyclic aromatic ring system, containing one or more heteroatoms, such as 1-10, e.g., 1-6, selected from O, S, and N, including, but not limited to, oxazolyl, oxadiazolyl, thiophenyl, thiadiazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridonyl, pyrimidonyl, quinolinyl, azaquinolyl, isoquinolinyl, azaisoquinolyl, quinazolinyl, azaquinazolinyl, benzozazoyl, azabenzoxazoyl, benzothiazoyl, or azabenzothiazoyl. The term "heterocycloalkyl" as used herein means a monocyclic or bicyclic 3-7 membered aliphatic heterocycle containing one or more heteroatoms, such as 1 to 7, e.g., 1 to 5, selected from O, S and N, including, but not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothipyranyl, or piperidonyl.

[0126] The terms "treatment" and "treating" as used herein 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 include the full range of treatments for a given condition suffered by a patient, including, for example, administering an active compound to alleviate symptoms or complications, delaying the progression of a disease, disorder or condition, alleviating or reducing symptoms or complications, and / or curing or eliminating a disease, disorder or condition, as well as preventing a condition, where prevention should be understood as the management and care of a patient for the purpose of combating a disease, condition or disorder, and includes administering an active compound to prevent the onset of symptoms or complications. Treatment can be performed in either an acute or chronic manner. The patient to be treated is preferably a mammal, particularly a human, but can also include animals such as dogs, cats, cows, sheep, pigs, etc.

[0127] The term "therapeutically effective amount" of the compound of formula (1) of the present invention as used herein means an amount sufficient to cure, alleviate or partially arrest the clinical symptoms of a given disease and its complications. The amount sufficient to achieve this is defined as a "therapeutically effective amount". The effective amount for each purpose depends on the severity of the disease or injury as well as the weight and general condition of the subject. It will be understood that the determination of the appropriate dosage can be achieved by using routine experimentation to construct a matrix of values ​​and testing different points in the matrix, all of which is within the ordinary skill of a trained physician or veterinarian.

[0128] In a further aspect, the present invention relates to a pharmaceutical composition comprising a compound of formula (1) and optionally a pharma- ceutically acceptable excipient, such as a carrier or diluent.

[0129] As used herein, "pharmaceutical acceptable excipients" includes, but is not limited to, carriers, excipients, diluents, adjuvants, colorants, flavorings, preservatives, and the like that one skilled in the art would consider using when formulating a compound of the present invention to make a pharmaceutical composition.

[0130] Adjuvants, diluents, excipients and / or carriers that can be used in the compositions of the present invention must be pharma- ceutically acceptable in the sense of being compatible with the compound of formula (1) and other components of the pharmaceutical composition, and not harmful to the recipient.Preferably, the compositions should not contain substances that can cause adverse reactions, such as allergic reactions.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.

[0131] As mentioned above, the compositions disclosed herein, particularly the pharmaceutical compositions, further comprise at least one pharma- ceutically acceptable adjuvant, diluent, excipient and / or carrier in addition to the compounds disclosed herein. In some embodiments, the pharmaceutical compositions comprise 1-99% by weight of at least one pharma- ceutically acceptable adjuvant, diluent, excipient and / or carrier and 1-99% by weight of the compounds disclosed herein. The total amount of the active ingredient and the pharma- ceutically acceptable adjuvant, diluent, excipient and / or carrier should not exceed 100% by weight of the composition, particularly the pharmaceutical composition.

[0132] In some embodiments, only one compound disclosed herein is used for the above purposes.

[0133] In some embodiments, two or more compounds disclosed herein are used in combination for the above purposes.

[0134] The compositions, particularly pharmaceutical compositions comprising the compounds described herein, can be adapted for oral, intravenous, topical, intraperitoneal, nasal, buccal, sublingual or subcutaneous administration, or for administration via the respiratory tract, for example in the form of an aerosol or fine powder suspended in the air. Thus, the pharmaceutical compositions can be in the form of, for example, tablets, capsules, powders, nanoparticles, crystals, amorphous materials, solutions, transdermal patches or suppositories.

[0135] Further embodiments of the processes are described in the Experimental Section herein, with each individual process and each starting material constituting an embodiment that may form part of an embodiment.

[0136] The above embodiments should be considered to refer to any one of the aspects described herein (e.g., "methods of treatment," "pharmaceutical compositions," "compounds for use as pharmaceuticals," or "compounds for use in a method," etc.), as well as any one of the embodiments described herein, unless an embodiment is specified to be directed to a particular aspect or aspects of the invention.

[0137] All references cited in this specification, including publications, patent applications, and patents, are hereby incorporated by reference to the same extent as if each reference was individually and specifically indicated to be incorporated by reference and was set forth in its entirety herein.

[0138] All headings and sub-headings are used herein for convenience only and should not be construed as limiting the invention in any way.

[0139] Any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or clearly contradicted by context.

[0140] As used in the context of describing the present invention, the terms "a" and "an" and "the" and similar referents should be construed to encompass both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0141] The recitation of ranges of values ​​herein is intended only to be used as a shorthand method of referring individually to each separate value within the range, unless otherwise indicated herein and each separate value is incorporated herein as if it were individually recited herein. Unless otherwise indicated, all exact values ​​provided herein represent corresponding approximations (e.g., all exact exemplary values ​​provided with respect to a particular factor or measurement can also be considered to provide corresponding approximate measurements modified by "about," as appropriate).

[0142] All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context.

[0143] The use of any and all examples or exemplary language (e.g., "etc.") provided herein is intended merely to better illustrate the invention and does not limit the scope of the invention unless otherwise indicated. No language in the specification should be construed as indicating any element as essential to the practice of the invention unless expressly stated.

[0144] The citation and incorporation of patent documents herein is for convenience only and does not reflect any opinion regarding the validity, patentability and / or enforceability of such patent documents.

[0145] As used herein, the term "and / or" is intended to refer to both alternatives as well as to each alternative individually. For example, the phrase "xxx and / or yyy" means "xxx and yyy," "xxx," or "yyy," with all three alternatives being subject to individual embodiments.

[0146] Description herein of any aspect or embodiment of the invention using terms such as "comprising," "having," "including," or "containing" with reference to one or more elements is intended to provide support for similar aspects or embodiments of the invention that "consist," "consist essentially of," or "substantially comprise" that particular element or elements, unless otherwise indicated or clearly contradicted by context (e.g., a composition described herein as comprising a particular element should be understood to also describe a composition consisting of that element, unless otherwise indicated or clearly contradicted by context). The present invention includes all modifications and equivalents of the subject matter recited in the aspects or claims presented herein to the maximum extent permitted by applicable law.

[0147] The present invention is further illustrated by the following examples which should not be construed as limiting the scope of protection. The features disclosed in the foregoing description and in the following examples may, both separately and in any combination thereof, be material for realizing the invention in diverse forms thereof.

[0148] Experimental procedure (evaluation of Kd value) The affinity of Examples 1-45 for galectins was determined by fluorescence anisotropy assay, and the compounds were used as inhibitors of the interaction between galectins and fluorescein-labeled saccharide probes (Sorme, P., Kahl-Knutsson, B., Huflejt, M., Nilsson, UJ, and Leffler H. (2004) "Fluorescence polarization as an analytical tool to evaluate galectin-ligand interactions", Anal. Biochem. 334:36-47 (Sorme et al. 2004); "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 (see Salomonsson et al. 2010)). [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10] [Table 1-11]

[0149] The group of compounds in the above table may have good intestinal uptake and good systemic and even CNS bioavailability in oral treatment. These compounds are considered as potential human drug candidates in the CNS as a treatment for neurodegenerative disorders such as dementia and Azheimers. [Table 2]

[0150] Several of the potentially CNS-available compounds listed above, Examples 2, 3, 6, 12, 15, 17, 32, 33, 34 and 35, have been shown to have low or no efflux and high uptake in in vitro cellular models of crossing the blood-brain barrier (BBB) ​​that are predictive of the availability of these compounds in the CNS. (Hellinger, E.; Veszelka, S.; Toth, AE; Walter, F.; Kittel, A.; Bakk, ML; Tihanyi, K.; Hada, V.; Nakagawa, S.; Duy, TDH; Niwa, M.; Deli, MA; Vastag, M. “Comparison of Brain Capillary Endothelial Cell-Based and Epithelial (MDCK-MDR1, Caco-2, and VB-Caco-2) Cell-Based Surrogate Blood-Brain Barrier Penetration Models)” Eur J Pharm Biopharm 2012, 82(2), 340-351).

[0151] In vivo mouse pharmacokinetic study of Example 35 Dosing Example 35 IV 1 mg / kg and PO 10 mg / kg results in excellent systemic bioavailability (Figure 1). Furthermore, good exposure in the brain is observed (Figure 2). The ratio between the exposure of Example 35 in the brain compared to plasma was calculated as AUC brain / AUC plasma = 0.19 (AUC = area under the curve). [Table 3] [Table 4]

[0152] Synthesis of Examples and Intermediates General Experiments: Nuclear magnetic resonance (NMR) spectra were recorded at 25° C. on a 400 MHz Varian instrument or a 500 MHz Bruker Avance Neo 500 instrument.

[0153] Chemical shifts are reported in ppm (d) using residual solvent as internal standard. Multiple peaks are designated as follows: s, singlet; d, doublet; dd, doublet of doublet; t, triplet; dt, triplet of triplet; q, quartet; m, multiplet; br s, broad singlet.

[0154] LC-MS were obtained on an Agilent 1100 HPLC coupled to an Agilent MSD mass spectrometer operating in ES(+) ionization mode. Column: Waters symmetry 2.1x30mm C18 or Chromolith RP-18 2x50mm. Solvent A water + 0.1% TFA and solvent B acetonitrile + 0.1% TFA. Wavelength 254nm.

[0155] Preparative HPLC was obtained on a Gilson system. Flow rate: 15 ml / min. Column: kromasil 100-5-C18 column. Wavelength: 220 nm. Solvent A water + 0.1% TFA and solvent B acetonitrile + 0.1% TFA.

[0156] The following abbreviations are used: aq: water-based Calcd: Calculated value CH3CN:Acetonitrile CuI: Copper iodide DCM: dichloromethane DIPEA: Diisopropylethylamine DMF: N,N-dimethylformamide ESI-MS: Electrospray ionization mass spectrometry Et3N: Triethylamine EtOAc: ethyl acetate h: time HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate HPLC: High-performance liquid chromatography LC: Liquid chromatography MeCN: Acetonitrile mL: milliliter MeOH: Methanol MeOD: deuterated methanol mm: millimeters mM: millimolar MS: Mass spectrometry nm: nanometer NaI: Sodium iodide NaOMe: Sodium methoxide N2: Nitrogen gas NMR: nuclear magnetic resonance Pd(dppf)Cl2: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) PE: Petroleum ether pH: acidity Prep: preparative rt: room temperature TBAF: Tetrabutylammonium fluoride TFA: Trifluoroacetic acid THF: tetrahydrofuran UV: Ultraviolet light Å: Angstrom

[0157] The following Examples 1-45 were prepared from Intermediates 1-44, respectively.

[0158] Example 1 3-Chlorophenyl 3-deoxy-3-[4-(3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 3-chlorophenyl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (30 mg, 0.069 mmol), (3-fluorophenyl)boronic acid (19 mg, 0.14 mmol), K2CO3 (38 mg, 0.28 mmol) and Pd(dppf)Cl2 (7.6 mg, 0.010 mmol) in dioxane / water (1 mL, 2:1) was stirred at 60 °C for 3 h. The mixture was concentrated and purified by Prep HPLC (C 18, H2O / MeCN / 0.1% TFA) to give the title compound (5 mg, 16%). ESI-MS m / z calculated [C 21 H 20 ClFN2O4S] [M+H] + : 451.1;Actual value: 450.7.

number

[0159] Example 2 5-Chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloropyridin-3-yl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (49 mg, 0.11 mmol), (4-chloro-3,5-difluorophenyl)boronic acid (43 mg, 0.22 mmol), K2CO3 (78 mg, 0.56 mg) and Pd(dppf)Cl2 (12 mg, 0.017 mmol) in 1,4-dioxane / water (1 mL, 2:1) was stirred at 90 °C for 4 h. The mixture was partitioned between EtOAc and water and the organic phase was dried and concentrated. Prep HPLC (C 18 The residue was purified by HPLC using 0.1% TFA (HO / MeCN / 0.1% TFA) to give the title compound (5 mg, 9%). ESI-MS m / z calculated [C 20 H 17Cl2F2N3O4S] [M+H] + :504.0;Actual value:503.8.

number

[0160] Example 3 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To Pd(dppf)Cl2 (18 mg, 0.024 mmol) was added 5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (90 mg, 0.16 mmol), (3,4,5-trifluorophenyl)boronic acid (56 mg, 0.32 mmol) and K2CO3 (177 mg, 1.28 mmol) in degassed water / dioxane (1:2, 1.5 mL). The mixture was stirred at 90 °C under argon for 3 h and then cooled to ambient temperature. NaOH (3M, 0.5 mL) was added and the mixture was stirred for 1 h. The mixture was diluted with water (10 mL) and extracted with DCM (3x10 mL). The organic phase was dried, concentrated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (24 mg, 31%). ESI-MS m / z calculated [C 20 H 17 ClF3N3O4S] [M+H] + : 488.1;Actual value: 488.1.

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[0161] Example 4 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,5-difluoro-4-methylphenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To Pd(dppf)Cl2 (16 mg, 0.021 mmol) was added 5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (80 mg, 0.14 mmol), 2-(3,5-difluoro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (59 mg, 0.23 mmol) and K2CO3 (157 mg, 1.14 mmol) in degassed water / dioxane (1:2, 1.5 mL). The mixture was stirred at 90 °C under argon for 3 h and then cooled to ambient temperature. NaOH (3 M, 0.5 mL) was added and the mixture was stirred for 1 h. The mixture was diluted with water (10 mL) and extracted with DCM (3x10 mL). The organic phase was dried, concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (34 mg, 49%). ESI-MS m / z calculated [C 21 H 20 ClF2N3O4S] [M+H] + : 484.1;Actual value: 484.1.

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[0162] Example 5 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A nitrogen-purged solution of 1,2,4,6-tetra-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranoside (250 mg, 0.52 mmol), (3,4,5-trifluorophenyl)boronic acid (184 mg, 1.05 mmol), K2CO3 (434 mg, 3.14 mmol) and Pd(dppf)Cl2 (58 mg, 0.079 mmol) in water / dioxane (1:2, 4 mL) was heated in a microwave reactor at 110° C. for 20 min. The mixture was partitioned between EtOAc and water, the organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc). The resulting material and PCl5 (52 mg, 0.25 mmol) were dissolved in DCM (1.5 mL) and BF3OEt2 (0.031 mL, 0.25 mmol) was added. The mixture was stirred at room temperature for 3 h, then diluted with DCM, washed with water and saturated aqueous NaHCO3, dried and evaporated. The residue was dissolved in 5-bromopyridine-3-thiol (37 mg, 0.19 mmol) in DMF (1 mL). K2CO3 (53 mg, 0.39 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was diluted with EtOAc, washed with water and brine, the organic phase was dried and evaporated. The residue was stirred in NaOMe (0.1 mL, 1 M) and MeOH (1 mL) at room temperature for 1 h. The reaction was quenched with acetic acid, concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (12 mg, 4%). ESI-MS m / z calculated [C 20 H 17 BrF3N3O4S][M+H] + :532.0;Actual value:531.7.

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[0163] Example 6 5-Bromopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-β-D-galactopyranosyl chloride (195 mg, 0.34 mmol), 5-bromopyridine-3-thiol (94 mg, 0.45 mmol) and Cs2CO3 (220 mg, 0.67 mmol) in DMF (2.0 mL) was stirred at room temperature for 20 h. The mixture was partitioned between EtOAc and brine, the organic phase was dried and evaporated and the residue was purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in MeOH (2.0 mL) and NaOMe (1M, 1.0 mL) at room temperature for 2 h. The reaction was neutralized with acetic acid (0.1 mL), evaporated and the residue purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (49 mg, 26%). ESI-MS m / z calculated [C 20 H 17 BrClF2N3O4S] [M+H] + :548.0;Actual value:547.8.

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[0164] Example 7 5-Ethynylpyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] 5-Bromopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (25 mg, 0.045 mmol), Pd(PPh3)2Cl2 (3.3 mg, 0.0045 mmol), CuI (1.0 mg, 0.0045 mol) were weighed into a flask, evacuated, and then flushed with nitrogen. THF (1.5 mL) and trimethylsilylacetylene (40 μL, 0.29 mmol) were added, followed by Et3N (0.2 mL). Nitrogen was bubbled through the mixture, then stirred at 50 °C for 19 h. The mixture was purified by passing through a silica column eluted with EtOAc, evaporated, and the residue was stirred in THF (1.0 mL) and TBAF (1.0 mL, 1 M in THF, 1.0 mmol) at room temperature for 10 min. The mixture was partitioned between water and EtOAc, the organic phase was evaporated, and the residue was purified by Prep HPLC (C 18 , H2O / MeCN / 0.1%TFA) to give the title compound (11 mg, 49%). ESI-MS m / z calculated [C 22 H 18 ClF2N3O4S] [M+H] + : 494.1;Actual value: 493.9.

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[0165] Example 8 5-Chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-β-D-galactopyranosyl chloride (200 mg, 0.34 mmol), 4-chloro-2-sulfanylbenzonitrile (221 mg, 1.04 mmol) and Cs2CO3 (549 mg, 1.69 mmol) in DMF (2.0 mL) was stirred at 40° C. for 40 h. The mixture was partitioned between EtOAc and brine, and the organic phase was dried and evaporated. The residue was stirred in pyridine (2.0 mL) and acetic anhydride (1.0 mL) for 18 h, then concentrated and purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in MeOH (4.0 mL) and NaOMe (1 M, 1.0 mL) at room temperature for 3.5 h. The reaction was neutralized with acetic acid (0.1 mL), evaporated, and the residue was purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (14 mg, 19%). ESI-MS m / z calculated [C 22 H 17 Cl2F2N3O4S] [M+H] + :528.0;Actual value:527.8.

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[0166] Example 9 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] Pd(dppf)Cl2 (23 mg, 0.03 mmol), (4-chloro-3,5-difluorophenyl)boronic acid (61 mg, 0.30 mmol) and K2CO3 (104 mg, 0.75 mmol) were weighed into a vial and flushed with nitrogen. A solution of 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (78 mg, 0.15 mmol) in dioxane (2.0 mL) was added to the vial followed by water (0.5 mL) and degassed with nitrogen. The mixture was stirred at 80 °C for 16 h and then partitioned between EtOAc and brine. The organic phase was evaporated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (4.3 g, 5%). ESI-MS m / z calculated [C 25 H 23 Cl2F2N3O5S] [M+H] + :586.1;Actual value:586.0.

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[0167] Example 10 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] Pd(dppf)Cl2 (20 mg, 0.026 mmol), (3,4,5-trifluorophenyl)boronic acid (47 mg, 0.26 mmol) and K2CO3 (90 mg, 0.65 mmol) were weighed into a vial and flushed with nitrogen. A solution of 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (67 mg, 0.13 mmol) in dioxane (1.5 mL) was added to the vial followed by water (0.75 mL) and degassed with nitrogen. The mixture was stirred at 80 °C for 18 h and then partitioned between EtOAc and brine. The organic phase was evaporated and the residue was purified by chromatography (SiO2, PE / EtOAc). The product was purified by Prep HPLC (C 18 Further purification by ESI-MS m / z calculated [C 25 H 23 ClF3N3O5S] [M+H] + :570.1;Actual value:570.0.

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[0168] Example 11 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A nitrogen purged solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside (500 mg, 0.95 mmol), K2CO3 (659 mg, 4.77 mmol), (3,4,5-trifluorophenyl)boronic acid (252 mg, 1.43 mmol) and Pd(dppf)Cl2 (105 mg, 0.14 mmol) in water / dioxane (1:2, 4.5 mL) was heated at 60° C. for 1 h. The mixture was partitioned between EtOAc and water, the organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc). The resulting material and PCl5 (206 mg, 0.99 mmol) were dissolved in DCM (8 mL) and BF3OEt2 (0.12 mL, 0.99 mmol) was added. The mixture was stirred at room temperature for 5 h, then diluted with DCM, washed with water and saturated aqueous NaHCO3, dried and evaporated. The residue was dissolved in 4-chloro-2-sulfanylbenzonitrile (161 mg, 0.95 mmol) in DMF (4 mL). K2CO3 (210 mg, 1.52 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was diluted with EtOAc, washed with water and brine, the organic phase was dried and evaporated. The residue was stirred in NaOMe (0.5 mL, 1 M) and MeOH (5 mL) at room temperature for 30 min. The reaction was concentrated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (31 mg, 6%). ESI-MS m / z calculated [C 22 H 17 ClF3N3O4S] [M+H] + :512.1;Actual value:512.3.

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[0169] Example 12 5-Chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A nitrogen purged solution of 2-bromo-5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (60.0 mg, 0.11 mmol), zinc cyanide (12.4 mg, 0.11 mmol), 1,1'-bis(diphenylphosphino)ferrocene (4.8 mg, 0.0085 mmol), tris(dibenzylideneacetone)dipalladium(0) (4.8 mg, 0.0085 mmol) and Zn (3.5 mg, 0.053 mmol) in DMF (1 mL) was stirred at 100° C. for 2 h. The mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried, concentrated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (6 mg, 11%). ESI-MS m / z calculated [C 21 H 16 ClF3N4O4S] [M+H] + :513.1;Actual value:512.8,

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[0170] Example 13 5-Chloro-2-cyanopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] A nitrogen purged solution of 2-bromo-5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (50 mg, 0.086 mmol), zinc cyanide (15.1 mg, 0.13 mmol), Zn (2.8 mg, 0.043 mmol), tris(dibenzylideneacetone)dipalladium(0) (3.9 mg, 0.0069 mmol) and 1,1'-bis(diphenylphosphino)ferrocene (3.9 mg, 0.0069 mmol) in DMF (2 mL) was stirred at 90° C. for 20 h. The mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried, concentrated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (2.9 mg, 6%) as a white solid. ESI-MS m / z calculated [C 21 H 17 Cl2F2N4O4S][M+H] + :529.0;Actual value:528.7.

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[0171] Example 14 5-Chloro-2-methylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A nitrogen purged solution of 5-chloro-2-methylpyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside (200 mg, 50% purity, 0.33 mmol), (3,4,5-trifluorophenyl)boronic acid (85.9 mg, 0.49 mmol), K2CO3 (225 mg, 1.63 mmol) and Pd(dppf)Cl2 (35.7 mg, 0.049 mmol) in dioxane (4 mL) and water (2 mL) was stirred at 60° C. for 6 h. The mixture was concentrated and the residue was dissolved in MeOH (10 mL) and NaOMe (1 mL, 1 M). After stirring at room temperature for 1 h, the reaction was quenched with acetic acid (0.1 mL). The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (6 mg, 4%) as a white solid. ESI-MS m / z calculated [C 22 H 20 F3N4O4S] [M+H] + : 493.1;Actual value: 492.9.

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[0172] Example 15 5-Bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromo-2-cyanopyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (453 mg, 0.66 mmol) in MeOH (12 mL), Et3N (3 mL) and water (1 mL) was stirred at room temperature for 16 h. The mixture was partitioned between EtOAc and water, the organic phase was dried and evaporated. The residue was recrystallized from EtOAc / PE (6 mL, 2:1) and the crystals were filtered off to give the title compound (167 mg, 45%). The filtrate was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (97 mg, 26%). ESI-MS m / z calculated [C 21 H 16 BrF3N4O4S][M+H] + :557.0;Actual:557.0.

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[0173] Example 16 2-Cyano-5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a nitrogen purged solution of 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (100 mg, 0.18 mmol), bis(triphenylphosphine)palladium(II) chloride (6.3 mg, 0.0090 mmol) and CuI (1.7 mg, 0.0090 mmol) in THF (2.0 mL) was added trimethylsilylacetylene (35 μL, 0.25 mmol) followed by DIPEA (44 μL, 0.25 mmol). The mixture was stirred at 50° C. for 20 h, cooled to room temperature, TBAF (0.3 mL, 1 M in THF, 0.3 mmol) was added and the mixture was stirred at room temperature for 10 min. The mixture was partitioned between EtOAc and water, and the organic phase was dried and evaporated. The residue was purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (39 mg, 43%). ESI-MS m / z calculated [C 23 H 17 F3N4O4S] [M+H] + :503.1;Actual value:503.1.

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[0174] Example 17 5-Chloropyridin-3-yl 3-[4-(4-chloro-3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] 4-Bromo-1-chloro-2-fluorobenzene (13 μL, 0.10 mmol), 5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (45 mg, 0.052 mmol) and tetrakis(triphenylphosphine)palladium(0) (6.0 mg, 0.0052 mmol) were dissolved in a degassed mixture of toluene (0.5 mL), EtOH (0.1 mL) and aqueous NaCO (52 μL, 2 M) and the resulting mixture was refluxed for 6 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), EtN (0.15 mL) and water (0.05 mL) and stirred at room temperature for 21 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (3 mg, 12%). ESI-MS m / z calculated [C 20 H 18 Cl2FN3O4S][M+H] + : 486.0;Actual value: 486.4.

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[0175] Example 18 5-Chloropyridin-3-yl 3-deoxy-3-[4-(6-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-α-D-galactopyranoside (97 mg, 0.11 mmol), (6-fluoro-2-pyridyl)boronic acid (31 mg, 0.22 mmol) and Pd(dppf)Cl2 (8.2 mg, 0.011 mmol) were dissolved in a degassed mixture of dioxane (1.0 mL), water (0.5 mL) and aqueous Na2CO3 (278 μL, 2 M). The mixture was stirred at 60 °C for 17 h. The mixture was filtered through celite, concentrated and the residue was dissolved in MeOH (1.0 mL), Et3N (0.15 mL) and water (0.05 mL) and stirred at room temperature for 5 h. The mixture was filtered and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (10 mg, 20%). ESI-MS m / z calculated [C 19 H 18 ClFN4O4S][M+H] + : 453.1;Actual value: 453.5.

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[0176] Example 19 5-Chloropyridin-3-yl 3-deoxy-3-[4-(5-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (100 mg, 0.16 mmol), tetrakis(triphenylphosphine)palladium(0) (19 mg, 0.016 mmol) and 2-bromo-5-fluoro-pyridine (87 mg, 0.49 mmol) were dissolved in a degassed mixture of toluene (1.0 mL), EtOH (0.2 mL) and aqueous Na2CO3 (246 μL, 2 M) and the mixture was refluxed for 2 h. The mixture was cooled to room temperature and the organic phase was separated. The aqueous phase was extracted with EtOAc (2×1 mL) and the combined organic phase was dried and concentrated. The residue was dissolved in MeOH (1.0 mL), EtN (0.15 mL) and water (0.05 mL) and stirred at 50° C. for 17 h. The mixture was filtered and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (33 mg, 44%). ESI-MS m / z calculated [C 19 H 18 ClFN4O4S][M+H] + : 453.1;Actual value: 453.0.

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[0177] Example 20 5-Chloropyridin-3-yl 3-deoxy-3-[4-(4-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (45 mg, 0.052 mmol), tetrakis(triphenylphosphine)palladium(0) (6.0 mg, 0.0052 mmol) and 2-bromo-4-fluoro-pyridine (35 μL, 0.33 mmol) were dissolved in a degassed mixture of toluene (1.0 mL), EtOH (0.2 mL) and aqueous NaCO (167 μL, 3 M) and the mixture was refluxed for 20 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), EtN (0.15 mL) and water (0.05 mL) and stirred at room temperature for 24 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (16 mg, 32%). ESI-MS m / z calculated [C 19 H 18 ClFN4O4S][M+H] + : 453.1;Actual value: 453.5.

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[0178] Example 21 5-Chloropyridin-3-yl 3-deoxy-3-[4-(1H-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-α-D-galactopyranoside (97 mg, 0.11 mmol), 1H-pyrazol-3-ylboronic acid (25 mg, 0.22 mmol) and Pd(dppf)Cl2 (8.2 mg, 0.011 mmol) were dissolved in a degassed mixture of dioxane (1.0 mL), water (0.5 mL) and aqueous Na2CO3 (278 μL, 2 M). The mixture was stirred at 60 °C for 17.5 h. More 1H-pyrazol-3-ylboronic acid (25 mg, 0.22 mmol) was added and the mixture was stirred at 80 °C for 23 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1%TFA). Further purification by chromatography (SiO2, EtOAc / MeOH) afforded the title compound (7 mg, 15%). ESI-MS m / z calculated [C 17 H 18 ClN5O4S] [M+H] + : 424.1;Actual value: 424.5.

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[0179] Example 22 5-Chloropyridin-3-yl 3-deoxy-3-[4-(1-methyl-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (97 mg, 0.11 mmol), tetrakis(triphenylphosphine)palladium(0) (12.9 mg, 0.011 mmol) and 3-bromo-1-methylpyrazole (22.6 μL, 0.22 mmol) were dissolved in a degassed mixture of toluene (1.0 mL), EtOH (0.2 mL) and aqueous NaCO (111 μL, 2 M) and the mixture was refluxed for 23 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), EtN (0.15 mL) and water (0.05 mL) and stirred at room temperature for 23 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (7.8 mg, 16%). ESI-MS m / z calculated [C 18 H 20 ClN5O4S] [M+H] + : 438.1;Actual value: 438.5.

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[0180] Example 23 5-Chloropyridin-3-yl 3-deoxy-3-[4-(1H-imidazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (97 mg, 0.11 mmol), tetrakis(triphenylphosphine)palladium(0) (12.9 mg, 0.011 mmol) and 2-bromo-1H-imidazole (32.7 mg, 0.22 mmol) were dissolved in a degassed mixture of toluene (1.0 mL), EtOH (0.2 mL) and aqueous NaCO (111 μL, 2 M) and the mixture was refluxed for 23 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), EtN (0.15 mL) and water (0.05 mL) and stirred at room temperature for 23 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (16 mg, 34%). ESI-MS m / z calculated [C 17 H 18 ClN5O4S] [M+H] + : 424.1;Actual value: 424.5.

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[0181] Example 24 5-Chloropyridin-3-yl 3-deoxy-3-[4-(oxazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (97 mg, 0.11 mmol), tetrakis(triphenylphosphine)palladium(0) (12.9 mg, 0.011 mmol) and 2-bromooxazole (32.9 mg, 0.22 mmol) were dissolved in a degassed mixture of toluene (1.0 mL), EtOH (0.2 mL) and aqueous Na2CO3 (111 μL, 2 M) and the mixture was refluxed for 23 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), Et3N (0.15 mL) and water (0.05 mL) and stirred at room temperature for 23 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1%TFA). Further purification by chromatography (SiO2, EtOAc / MeOH) afforded the title compound (15.8 mg, 33%). ESI-MS m / z calculated [C 17 H 17 ClN4O5S] [M+H] + : 425.1;Actual value: 425.5.

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[0182] Example 25 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (45 mg, 0.052 mmol), tetrakis(triphenylphosphine)palladium(0) (6.0 mg, 0.0052 mmol) and 4-bromothiazal (9.2 μL, 0.10 mmol) were dissolved in a degassed mixture of toluene (0.5 mL), EtOH (0.1 mL) and aqueous Na2CO3 (52 μL, 2 M) and the mixture was refluxed for 6 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), Et3N (0.15 mL) and water (0.05 mL) and stirred at room temperature overnight. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (6.0 mg, 26%). ESI-MS m / z calculated [C 17 H 17 ClN4O4S2] [M+H] + : 441.0;Actual value: 441.5.

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[0183] Example 26 5-Chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (45 mg, 0.052 mmol), tetrakis(triphenylphosphine)palladium(0) (6.0 mg, 0.0052 mmol) and 2-bromothiazal (9.2 μL, 0.10 mmol) were dissolved in a degassed mixture of toluene (0.5 mL), EtOH (0.1 mL) and aqueous Na2CO3 (52 μL, 2 M) and the mixture was refluxed for 6 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), Et3N (0.15 mL) and water (0.05 mL) and stirred at room temperature overnight. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (7.0 mg, 31%). ESI-MS m / z calculated [C 17 H 17 ClN4O4S2] [M+H] + : 441.0;Actual: 441.0.

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[0184] Example 27 5-Chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (45 mg, 0.052 mmol), tetrakis(triphenylphosphine)palladium(0) (6.0 mg, 0.0052 mmol) and 2-bromo-4-chlorothiazole (21 mg, 0.10 mmol) were dissolved in a degassed mixture of toluene (0.5 mL), EtOH (0.1 mL) and aqueous Na2CO3 (52 μL, 2 M) and the mixture was refluxed for 16 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), Et3N (0.15 mL) and water (0.05 mL) and stirred at room temperature for 3 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (11 mg, 45%). ESI-MS m / z calculated [C 17 H 16 Cl2N4O4S2] [M+H] + : 475.0;Actual value: 474.7.

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[0185] Example 28 5-Bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] 5-Bromopyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (189 mg, 0.29 mmol), tetrakis(triphenylphosphine)palladium(0) (33 mg, 0.029 mmol) and 2-bromo-4-chlorothiazole (115 mg, 0.58 mmol) were dissolved in a degassed mixture of toluene (2.0 mL), EtOH (0.4 mL) and aqueous Na2CO3 (217 μL, 2 M) and the mixture was refluxed for 19 h. The mixture was diluted with water (10 mL), filtered and extracted with EtOAc (2x10 mL). The combined organic phase was concentrated and the residue was stirred in MeOH (2 mL) and NaOMe (0.1 mL, 1 M) at room temperature for 2 h. The reaction was quenched with acetic acid, concentrated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (16 mg, 10%). ESI-MS m / z calculated [C 17 H 16 BrClN4O4S2] [M+H] + :519.0;Actual value:518.8.

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[0186] Example 29 5-Chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] 5-Chloro-2-cyanophenyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (92 mg, 0.15 mmol), tetrakis(triphenylphosphine)palladium(0) (17 mg, 0.015 mmol) and 2-bromo-4-chlorothiazole (58 mg, 0.29 mmol) were dissolved in a degassed mixture of toluene (1.0 mL) and aqueous Na2CO3 (109 μL, 2 M) and the mixture was refluxed for 22 h. The mixture was diluted with water (2 mL), filtered and extracted with EtOAc (2×5 mL). The combined organic phase was concentrated and the residue was stirred in MeOH (1 mL) and NaOMe (15 μL, 1 M) at room temperature for 1 h. The reaction was quenched with acetic acid, concentrated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (12 mg, 13%). ESI-MS m / z calculated [C 19 H 16 Cl2N4O4S2] [M+H] + : 499.0;Actual value: 498.7.

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[0187] Example 30 5-Chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] 5-Chloro-2-cyanopyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (23 mg, 0.036 mmol), tetrakis(triphenylphosphine)palladium(0) (4.2 mg, 0.0036 mmol) and 2-bromo-4-chlorothiazole (14 mg, 0.073 mmol) were dissolved in a degassed mixture of toluene (0.25 mL), EtOH (0.05 mL) and aqueous NaCO (27 μL, 2 M) and the mixture was refluxed for 10 h. The mixture was concentrated, dissolved in MeOH (1.0 mL), EtN (0.15 mL) and water (0.05 mL) and stirred at room temperature for 1 h. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (2.5 mg, 14%). ESI-MS m / z calculated [C 18 H 15 Cl2N5O4S2] [M+H] + :500.0;Actual value:499.8.

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[0188] Example 31 5-Chloropyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(2-benzyloxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (77 mg, 0.11 mmol) and palladium on carbon (10 mg, 0.094 mmol) in MeOH (1.0 mL) was subjected to hydrogen gas (1 atm). The mixture was heated at 50° C. for 2 h, cooled to room temperature, and filtered. NaOMe (0.2 mL, 1 M) was added to the filtrate, which was stirred at room temperature for 100 min. Acetic acid (50 μL) was added and the mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (11 mg, 21%). ESI-MS m / z calculated [C 17 H 17 ClN4O5S2] [M+H] + : 457.0;Actual: 457.0.

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[0189] Example 32 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (183 mg, 0.38 mmol), benzaldehyde dimethyl acetal (114 μL, 0.75 mmol) and p-toluenesulfonic acid monohydrate (30 mg, 0.14 mmol) in MeCN (2.0 mL) was stirred at room temperature for 72 hours. Further benzaldehyde dimethyl acetal (114 μL, 0.75 mmol) and p-toluenesulfonic acid monohydrate (30 mg, 0.14 mmol) were added and the mixture was stirred at room temperature for 1 hour. Et3N (100 μL, 0.73 mmol) was added followed by water and PE and the precipitate was isolated by filtration. The mixture was partitioned between EtOAc and saturated aqueous NaHCO3, the organic phase was evaporated and purified by chromatography (SiO2, PE / EtOAc). The resulting material and NaH (60% in oil, 16 mg, 0.4 mmol) were stirred in DMF (2.0 mL) for 5 min, then iodomethane (17 μL, 0.27 mmol) was added. After stirring at room temperature for 30 min, water was added and the precipitate was isolated and triturated in MeOH. The resulting material was stirred in 80% aqueous TFA (2.0 mL) at room temperature for 30 min. Ice and PE were added and the supernatant was decanted. The residue was partitioned between EtOAc and water and the pH was adjusted to about 7 with NaOH (1 M). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc). The product was triturated in PE / EtOAc (1:1) to give the title compound (54 mg, 29%). ESI-MS m / z calculated [C 21 H 19 ClF3N3O4S] [M+H] + :502.1;Actual value:502.1.

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[0190] Example 33 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (305 mg, 0.57 mmol), benzaldehyde dimethyl acetal (182 μL, 1.2 mmol) and p-toluenesulfonic acid monohydrate (30 mg, 0.14 mmol) in MeCN (4.0 mL) was stirred at room temperature for 20 h. Et3N (100 μL, 0.73 mmol) was added followed by water (2.0 mL) and the precipitate was isolated by filtration and the cake was washed with water and PE. The resulting solid and NaH (60% in oil, 30 mg, 0.71 mmol) were stirred in DMF (4.0 mL) for 5 min, followed by the addition of iodomethane (30 μL, 0.47 mmol). After stirring at room temperature for 30 min, water was added and the precipitate was isolated by filtration. The precipitate was recrystallized in EtOAc / PE (1:2) and the crystals were isolated. The crystals were stirred in 80% aqueous TFA (2.0 mL) at room temperature for 30 min. Ice and PE were added and the supernatant was decanted. The residue was partitioned between EtOAc and water and the pH was adjusted to about 7 with NaOH (1 M). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the title compound (124 mg, 40%). ESI-MS m / z calculated [C 21 H 19 BrF3N3O4S][M+H] + :546.0;Actual:546.0.

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[0191] Example 34 5-Ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (90 mg, 0.17 mmol) in THF (2.0 mL) was added to a mixture of CuI (2.0 mg, 0.0086 mmol) and bis(triphenylphosphine)palladium(II) chloride (6.3 mg, 0.0086 mmol) under nitrogen. DIPEA (41 μL, 0.23 mmol) was added followed by trimethylsilylacetylene (38 μL, 0.25 mmol) and the mixture was stirred at 50 °C for 48 h. The mixture was purified by chromatography (SiO2, PE / EtOAc) and then triturated from PE / EtOAc (1:1). The resulting material was stirred in THF (2.0 mL) and TBAF (1.0 mL, 1 M in THF, 1.0 mmol) for 45 min. The mixture was partitioned between EtOAc, water and NaOH (1 mL, 1 M). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the title compound (23 mg, 28%). ESI-MS m / z calculated [C 23 H 20 F3N3O4S] [M+H] + : 492.1;Actual value: 492.1.

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[0192] Example 35 5-Chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A nitrogen purged solution of 2-bromo-5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside (124 mg, 0.21 mmol), 1,1'-bis(diphenylphosphino)ferrocene (9.6 mg, 0.017 mmol), zinc cyanide (25.1 mg, 0.21 mmol), tris(dibenzylideneacetone)dipalladium(0) (7.8 mg, 0.0085 mmol) and Zn (7.0 mg, 0.11 mmol) in DMF (2.77 mL) was stirred at 100 °C for 1 h. Additional zinc cyanide (25.1 mg, 0.21 mmol), Zn (7.0 mg, 0.11 mmol), 1,1'-bis(diphenylphosphino)ferrocene (9.6 mg, 0.017 mmol) and tris(dibenzylideneacetone)dipalladium(0) (7.8 mg, 0.0085 mmol) were added and the mixture was stirred at 100° C. for 30 min. The mixture was cooled to room temperature, diluted with EtOAc (30 mL) and washed with water (5×30 mL) and brine (30 mL). The organic phase was dried, concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (22 mg, 20%). ESI-MS m / z calculated [C 22 H 18 ClF3N4O4S] [M+H] + :527.1;Actual value:526.8,

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[0193] Example 36 5-Chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,3-imidazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of N-[p-tolylsulfonyl-(3,4,5-trifluorophenyl)methyl]formamide (54 mg, 0.16 mmol) in 1,2-dimethoxyethane (4.5 mL) was cooled to -10 °C. To this solution was added phosphorus(V) oxychloride (36 μL, 0.39 mmol), followed by dropwise addition of Et3N (0.11 mL, 0.79 mmol) in 1,2-dimethoxyethane (0.5 mL). The mixture was allowed to reach room temperature in 1 h and then stirred at room temperature for an additional 2 h. The mixture was partitioned between water and EtOAc. The organic phase was washed with saturated aqueous NaHCO3, dried and evaporated to give crude 1,2,3-trifluoro-5-[isocyano(p-tolylsulfonyl)methyl]benzene. A solution of 5-chloropyridin-3-yl 3-amino-3-deoxy-1-thio-α-D-galactopyranoside (40 mg, 0.13 mmol), 2-oxoacetic acid (8.7 mg, 0.012 mmol) and K2CO3 (90 mg, 0.65 mmol) in DMF (0.6 mL) was stirred at room temperature for 2 h. Then, crude 1,2,3-trifluoro-5-[isocyano(p-tolylsulfonyl)methyl]benzene dissolved in DMF (0.1 mL) was added and the resulting mixture was stirred at room temperature for 19 h. The mixture was partitioned between water and EtOAc, and the organic phase was dried and evaporated. The residue was purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (13 mg, 17%) as the TFA salt. ESI-MS m / z calculated [C 20 H 17 ClF3N3O4S] [M+H] + : 488.1; Actual value: 488.1,

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[0194] Example 37 5-Chloro-[3,3-bis(hydroxymethyl)azetidin-1-yl]pyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a nitrogen purged solution of 5-chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptanyl}-pyridin-3-yl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (42 mg, 0.079 mmol), Pd(dppf)Cl2 (9.5 mg, 0.013 mmol) and K2CO3 (45 mg, 0.32 mmol) in dioxane (1.5 mL) and water (0.75 mL) was added (3,4,5-trifluorophenyl)boronic acid (24 mg, 0.13 mmol) and the mixture was stirred at 80 °C for 18 h. The mixture was filtered through silica and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (1.1 mg, 2%). ESI-MS m / z calculated [C 25 H 26 ClF3N4O6S] [M+H] + :586.1;Actual value:586.0.

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[0195] Example 38 5-Chloropyridin-3-yl 3-deoxy-3-[3-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A nitrogen purged solution of 5-chloropyridin-3-yl 3-deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-2-O-methyl-1-thio-α-D-galactopyranoside (20 mg, 0.040 mmol), (3,4,5-trifluorophenyl)boronic acid (11 mg, 0.060 mmol), Pd(dppf)Cl2 (4.4 mg, 0.0060 mmol) and K2CO3 (28 mg, 0.20 mmol) in dioxane (0.5 mL) and water (0.25 mL) was stirred at 60 °C for 1 h. The mixture was partitioned between EtOAc and water. The organic phase was dried, evaporated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (12 g, 60%). ESI-MS m / z calculated [C 21 H 19 ClF3N3O4S] [M+H] + :502.1;Actual value:502.1.

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[0196] Example 39 3,4-Dichlorophenyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 3,4-dichlorophenyl 2,4-di-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-1-thio-α-D-galactopyranoside (40 mg, 0.066 mmol) in MeOH (10 mL), Et3N (0.184 mL) and water (0.5 mL) was stirred at room temperature overnight. The mixture was filtered and purified by Prep HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (17 mg, 50%). ESI-MS m / z calculated [C 21 H 16Cl2F3NO5S][M+H] + :522.0;Actual:522.0.

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[0197] Example 40 3,4-Dichlorophenyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 3,4-dichlorophenyl 2,4-di-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-1-thio-α-D-galactopyranoside (15 mg, 0.024 mmol) in MeOH (5 mL), Et3N (0.10 mL) and water (0.5 mL) was stirred at room temperature overnight. The mixture was filtered and the filtrate was purified by Prep HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give the title compound (2.5 mg, 19%). ESI-MS m / z calculated [C 21 H 16 Cl2F3NO4S2] [M+H] + :538.0;Actual:538.0.

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[0198] Example 41 3,4-Dichlorophenyl-3-deoxy-3-[5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 3,4-dichlorophenyl 2,4-di-O-acetyl-3-deoxy-3-[(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-1-thio-D-galactopyranoside (19 mg, 0.031 mmol) in MeOH (1 mL), Et3N (0.5 mL) and water (0.25 mL) was stirred at room temperature overnight. The mixture was filtered and purified by Prep HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254). The product was further purified by preparative SFC to give the title compound (3.4 mg, 21%). ESI-MS m / z calculated [C 20 H 15 Cl2F3N2O5S] [M+H] + :523.0;Actual:523.0.

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[0199] Example 42 3,4-Dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 3,4-dichlorophenyl 3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-2-O-methyl-1-thio-α-D-galactopyranoside (100 mg, 0.19 mmol), 2-(2-benzyloxythiazol-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (112 mg, 0.28 mmol), and K2CO3 (130 mg, 0.94 mmol) in dioxane (1.5 mL) and water (0.75 mL) was degassed with nitrogen, followed by addition of Pd(dppf)Cl2 (28 mg, 0.038 mmol) and stirring at 60 °C for 1 h. The mixture was partitioned between EtOAc and brine. The organic phase was dried, evaporated, and purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in DCM (1.0 mL) and TFA (150 μL) at room temperature for 1 h. The mixture was partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the title compound (28 mg, 29%). ESI-MS m / z calculated [C 19 H 19 Cl2N3O5S2] [M+H] + :504.0;Actual:504.0.

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[0200] Example 43 3,4-Dichlorophenyl 3-[4-(2-aminothiazol-4-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To an argon-degassed solution of 3,4-dichlorophenyl 3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside (39 mg, 0.073 mmol), [2-(tert-butoxycarbonylamino)thiazol-4-yl]boronic acid (18 mg, 0.073 mmol), tris(dibenzylideneacetone)dipalladium(0) (6.6 mg, 0.0073 mmol) and 1,1'-bis(diphenylphosphino)ferrocene (8.2 mg, 0.015 mmol) in dioxane (0.5 mL), K2CO3 (72.5 μL, 2 M, 0.15 mmol) and water (0.18 mL) were added and the mixture was stirred at 60° C. for 1 h. The mixture was diluted with water and extracted twice with EtOAc. The organic phase was dried, evaporated, and dissolved in DCM (1.0 mL) and TFA (1.0 mL). The mixture was stirred at room temperature for 1 h and then concentrated. The residue was purified by reverse phase chromatography (C 18 , H2O / MeCN / 0.1% TFA) to give the title compound (1.8 mg, 5%). ESI-MS m / z calculated [C 19 H 20 Cl2N4O4S2] [M+H] + :503.0;Actual value:502.8.

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[0201] Example 44 5-Chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside [ka] Pd(dppf)Cl2 (6 mg, 0.0082 mmol), (4-chloro-3,5-difluorophenyl)boronic acid (15 mg, 0.076 mmol), 5-chloro-2-cyanophenyl 4,6-O-benzylidene-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-2-O-methyl-1-thio-α-D-galactopyranoside (31 mg, 0.050 mmol) and K2CO3 (35 mg, 0.25 mmol) were weighed into a vial and flushed with nitrogen. Dioxane (2.0 mL) was added to the vial followed by water (1.0 mL) and degassed with nitrogen. The mixture was stirred at 60° C. for 2 h and then partitioned between EtOAc and brine. The organic phase was evaporated and the residue was purified by filtration through silica using EtOAc / DCM. The resulting material was stirred in TFA / water (0.5 mL, 4:1) at room temperature for 20 min. The mixture was neutralized with NaOH (1M) and extracted twice with EtOAc. The organic phase was dried, evaporated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1%TFA). The product was further purified by chromatography (SiO2, PE / EtOAc) to give the title compound (6.0 mg, 22%). ESI-MS m / z calculated [C 23 H 19 Cl2F2N3O4S] [M+H] + :542.0;Actual:542.0.

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[0202] Example 45 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] Pd(dppf)Cl2 (6 mg, 0.0082 mmol), (4-chloro-3,5-difluorophenyl)boronic acid (15 mg, 0.076 mmol), 5-chloro-2-cyanophenyl 4,6-O-benzylidene-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-2-O-methyl-1-thio-α-D-galactopyranoside (31 mg, 0.050 mmol) and K2CO3 (35 mg, 0.25 mmol) were weighed into a vial and flushed with nitrogen. Dioxane (2.0 mL) was added to the vial followed by water (1.0 mL) and degassed with nitrogen. The mixture was stirred at 60 °C for 2 h and then partitioned between EtOAc and brine. The organic phase was evaporated and the residue was purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in TFA / water (0.5 mL, 4:1) at room temperature for 20 min. The mixture was neutralized with NaOH (1M) and extracted twice with EtOAc. The organic phase was dried, evaporated and analyzed by Prep HPLC (C 18 , H2O / MeCN / 0.1%TFA). The product was further purified by chromatography (SiO2, PE / EtOAc) to give the title compound (6.5 mg, 25%). ESI-MS m / z calculated [C 23 H 19 ClF3N3O4S] [M+H] + :526.1;Actual value:526.1.

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[0203] Intermediate 1 3-(4-Bromo-1H-pyrazol-1-yl)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose [ka] A solution of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (5.00 g, 19.2 mmol) in DCM (100 mL) and pyridine (3.1 mL, 38.4 mmol) was cooled to 0 °C and trifluoromethanesulfonic anhydride (3.9 mL, 23.1 mmol) in DCM (20 mL) was added dropwise. After stirring at 10 °C for 1 h, the mixture was quenched by adding crushed ice. The mixture was partitioned between DCM and HCl (1 M) and the organic phase was washed with saturated aqueous NaHCO3, dried and concentrated. To the crude product and Cs2CO3 (6.25 g, 19.2 mmol) in DMF (60 mL) was added 4-bromopyrazole (5.65 g, 38.4 mmol). After stirring at room temperature for 18 h, ice was added to the mixture and the solid was filtered off, washed with 33% aqueous MeOH, and then dried to give the product (7.29 g, 97%). ESI-MS m / z calculated [C 15 H 21 BrN2O5] [M+H] + : 389.1;Actual value: 388.8.

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[0204] 1,2,4,6-Tetra-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranoside [ka] 3-(4-Bromo-1H-pyrazol-1-yl)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose (6.00 g, 15.4 mmol) was dissolved in TFA (24 mL) and water (96 mL) and stirred at room temperature for 3 h. The mixture was evaporated using MeCN to azeotropically remove water and TFA, and finally treated in vacuum for 1 h. The crude product was dissolved in EtOAc (30 mL). Et3N (23.5 mL, 167 mmol) was added, maintaining the temperature at 40° C., and acetic anhydride (13.3 mL, 139 mmol) was added at a rate that maintained the same temperature. The mixture was stirred at 40° C. for 6 h and at room temperature for 72 h, then cooled to 0° C. HCl (42 mL, 2 M, 84 mmol) was added slowly, and the mixture was partitioned between EtOAc and water. The organic phase was washed with saturated aqueous NaHCO3, then with brine. The organic phase was evaporated and the residue was stirred in EtOAc (10 mL) and PE (20 mL). The precipitate was isolated by filtration, washed with EtOAc / PE (1:4) and dried to give the product (1.79 g, 27%). ESI-MS m / z calculated [C 17 H 21 BrN2O9][M-AcOH] + : 417.0;Actual value: 416.6.

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[0205] 3-Chlorophenyl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranoside (615 mg, 1.29 mmol) and PCl5 (349 mg, 1.68 mmol) in DCM (8 mL) was added BF3OEt2 (0.26 mL, 2.15 mmol) and the resulting mixture was stirred at room temperature for 24 h. The solution was washed with ice / water and the organic phase was washed with saturated aqueous NaHCO3, dried and evaporated. The crude product and 3-chlorobenzenethiol (0.12 mL, 1.00 mmol) were dissolved in DMF (5 mL), NaH (60% in oil, 77 mg, 2.00 mmol) was added and the mixture was stirred at room temperature for 3 h. The mixture was diluted with EtOAc, washed twice with water and once with brine, and the organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give a mixture of products. The resulting material was stirred in MeOH (4 mL) and NaOMe (1M, 0.5 mL) at room temperature for 1 h. The mixture was quenched with AcOH, concentrated and purified by HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the product (68 mg, 12%). ESI-MS m / z calculated [C 15 H 16 BrClNO4S] [M+H] + : 435.0;Actual value: 434.6.

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[0206] Intermediate 2 5-Chloropyridin-3-yl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranoside (930 mg, 1.95 mmol) and PCl5 (528 mg, 2.53 mmol) in DCM (15 mL) was added BF3OEt2 (0.31 mL, 2.53 mmol) and the resulting mixture was stirred at room temperature for 5 h. The solution was washed with ice / water and the organic phase was washed with saturated aqueous NaHCO3, dried and evaporated. The residue was dissolved in 5-chloropyridine-3-thiol (213 mg, 1.46 mmol) in DMF (7 mL), NaH (60% in oil, 112 mg, 2.92 mmol) was added and the mixture was stirred at room temperature for 16 h. The mixture was diluted with EtOAc and washed twice with water and once with brine. The organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in NaOMe (0.5 mL, 1M) and MeOH (6 mL) at room temperature for 1 h. The reaction was quenched with AcOH, evaporated and purified by HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the product (49 mg, 6%). ESI-MS m / z calculated [C 14 H 15 BrClN3O4S] [M+H] + : 436.0;Actual value: 435.6.

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[0207] Intermediate 3 2,4,6-Tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranosyl chloride [ka] 1,2,4,6-Tetra-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranoside (2.0 g, 4.06 mmol) and PCl5 (1.73 g, 8.12 mmol) were stirred in DCM (30 mL) and BF3OEt2 (0.65 mL, 5.30 mmol) was added. The mixture was stirred at room temperature for 4 h, further BF3OEt2 (0.33 mL, 2.64 mmol) was added and stirring was continued at room temperature for 2 h. The mixture was partitioned between ice, water, NaOH (10 mL, 5 M) and DCM, the organic phase was separated, dried and evaporated to give the product (1.92 g, quantitative yield).

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[0208] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside [ka] NaH (60% in oil, 50 mg, 1.31 mmol) was added to 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranosyl chloride (495 mg, 1.09 mmol) and 5-chloropyridine-3-thiol (159 mg, 1.09 mmol) in DMF (5 mL). The mixture was stirred at room temperature for 21 h. Further 5-chloropyridine-3-thiol (80 mg, 0.55 mmol) and NaH (60% in oil, 25 mg, 0.55 mmol) were added and the mixture was stirred for another 4 h before being diluted with EtOAc (50 mL) and washed with water (5×50 mL) and brine (50 mL). The organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (148 mg, 24%). ESI-MS m / z calculated value [C 20 H 22 BrClN3O7S] [M+H] +:562.0;Actual value:562.1.

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[0209] Intermediate 6 3-Deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose [ka] A solution of 1,2:5,6-di-O-isopropylidene-α-D-glucuronose (12.54 g, 48.2 mmol) in DCM (150 mL) and pyridine (7.8 mL, 96.4 mmol) was cooled to 0 °C and trifluoromethanesulfonic anhydride (9.8 mL, 57.9 mmol) in DCM (30 mL) was added dropwise. After stirring at 10 °C for 1 h, the mixture was quenched by adding crushed ice. The mixture was partitioned between DCM and HCl (1 M) and the organic phase was washed with saturated aqueous NaHCO3, dried and concentrated. To a solution of the crude product and Cs2CO3 (15.7 g, 48.2 mmol) in DMF (150 mL) was added 4-iodopyrazole (13.36 g, 67.5 mmol). After stirring at room temperature for 2 h, ice was added to the mixture and the solid was filtered off, washed with 33% aqueous MeOH, and then dried to give the product (23.9 g, quantitative yield). ESI-MS m / z calculated [C 15 H 21 IN2O5] [M+H] + : 437.1;Actual value: 436.9.

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[0210] 1,2,4,6-Tetra-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside [ka] 3-Deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose (6.00 g, 15.4 mmol) was dissolved in TFA (40 mL) and water (100 mL) and stirred at room temperature for 1 h. The mixture was evaporated using MeCN to azeotropically remove water and TFA and finally worked up in vacuum. The crude product was dissolved in EtOAc (105 mL), Et3N (105 mL) and acetic anhydride (53 mL, 560 mmol) were added and the mixture was stirred at room temperature for 20 h. The mixture was cooled to 0° C. and EtOAc (200 mL) was added slowly followed by HCl (280 mL, 2 M). The mixture was stirred for 20 min and then filtered through celite. The organic phase was separated, washed with saturated aqueous NaHCO3 and brine, dried and evaporated. The residue was filtered through silica using EtOAc / PE (1:1) and concentrated. The resulting syrup was dissolved in EtOAc (50 mL) and PE (80 mL) was added slowly to induce crystallization. The crystals were isolated by filtration to give the product (9.68 g, 58% purity, 38%). The filtrate was evaporated to give more product (15.8 g, 65% purity, 62%). ESI-MS m / z calculated [C 17 H 21 IN2O9] [M+H] + :525.0;Actual value:524.8.

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[0211] 1,2,4,6-Tetra-O-acetyl-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-β-D-galactopyranoside [ka] Pd(dppf)Cl2 (582 mg, 0.76 mmol), 1,2,4,6-tetra-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside (2.2 g, 3.78 mmol), K2CO3 (2.61 g, 18.9 mmol) and (4-chloro-3,5-difluorophenyl)boronic acid (994 mg, 4.9 mmol) were weighed into a flask and flushed with nitrogen. Dioxane (10 mL) was added to the flask followed by water (5.0 mL) and degassed with nitrogen. The mixture was stirred at 60 °C for 1 h and then partitioned between EtOAc and brine. The organic phase was evaporated and the residue was purified by chromatography (SiO2, PE / EtOAc) to give the product (1.03 g, 77%). ESI-MS m / z calculated [C 23 H 23 ClF2N2O9] [M+H] + :545.1;Actual value:544.9.

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[0212] 2,4,6-Tri-O-acetyl-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-β-D-galactopyranosyl chloride [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-β-D-galactopyranoside (1.022 g, 1.87 mmol) and PCl5 (996 mg, 4.7 mmol) in DCM (10 mL), BF3OEt2 (0.48 mL, 3.74 mmol) was added and the mixture was stirred at room temperature for 2.5 h. The solution was partitioned between DCM and ice / water / NaOH (2 M). The organic phase was dried and evaporated to give the product (1.34 g, quantitative yield).

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[0213] Intermediate 9 5-Chloro-2-cyanophenyl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside [ka] 2,4,6-Tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranosyl chloride (1.00 g, 1.32 mmol), 4-chloro-2-sulfanylbenzonitrile (314 mg, 1.85 mmol) and K2CO3 (360 mg, 2.6 mmol) were stirred in DMF (8.0 mL) at 60 °C for 2 h. The mixture was partitioned between EtOAc / water / HCl and the organic phase was collected, dried and evaporated. The residue was purified by chromatography (SiO2, PE / EtOAc) and the resulting material was stirred in MeOH (4 mL) and NaOMe (1 M, 0.5 mL) at room temperature for 18 h. The reaction was neutralized with acetic acid (60 μL), evaporated and the residue purified by Prep HPLC (C 18 , HO / MeCN / 0.1% TFA) to give the product (80 mg, 13%). ESI-MS m / z calculated [C 16 H 15 BrClN3O4S] [M+H] + : 460.0;Actual value: 459.7.

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[0214] 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside [ka] A mixture of 5-chloro-2-cyanophenyl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (302 mg, 0.65 mmol) in EtOH (8.0 mL) and NaOH (3M, 4.0 mL) was stirred at 50° C. for 17 h. The mixture was stirred at 70° C. for 2 h, then concentrated and partitioned between EtOAc / water / HCl at pH 1-2. The organic phase was dried, evaporated and the residue was purified by chromatography (SiO2, PE / EtOAc). The resulting material, 1-hydroxybenzotriazole hydrate (147 mg, 0.93 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (183 mg, 0.93 mmol) were stirred in DMF (4 mL) and azetidine (91 μL, 1.24 mmol) was added followed by Et3N (91 μL, 0.62 mmol). The mixture was stirred at room temperature for 18 h and then partitioned between brine and EtOAc. The aqueous phase was extracted three times with EtOAc and the combined organic phases were dried, evaporated and purified by chromatography (SiO2, EtOAc / MeOH) to give the product (157 mg, 49%). ESI-MS m / z calculated [C 19 H 21 BrClN3O4S] [M+H] + :518.0;Actual value:517.8.

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[0215] Intermediate 12 2-Bromo-5-chloro-pyridine-3-thiol [ka] To an ice-cold solution of 2-bromo-5-chloro-3-fluoro-pyridine (2.00 g, 9.5 mmol) in DMF (10 mL) was added sodium hydrosulfide hydrate (682 mg, 8.5 mmol). After 2 h at room temperature, the mixture was partitioned between diethyl ether and HCl (0.5 M). The organic phase was extracted with NaOH (0.5 M). The aqueous phase was acidified with HCl (5 M) until a precipitate formed. The product was obtained by filtration (735 mg, 34%). ESI-MS m / z calculated [C5H4BrClNS] [M+H] + :223.9;Actual value:223.6.

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[0216] 2,4,6-Tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranosyl chloride [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside (7.74 g, 14.7 mmol), PCl5 (6.28 g, 29.5 mmol) in DCM (100 mL) was added BF3OEt2 (3.95 mL, 29.5 mmol). The mixture was stirred at room temperature for 4 h, then partitioned between ice / water and DCM, and NaOH (85 mL, 2 M) was added, washing to a pH of about 5. The organic phase was dried and evaporated to give the product (6.2 g, 60% pure), which was used in the subsequent step without purification.

[0217] 2-Bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranosyl chloride (2.20 g, 60% purity, 2.63 mmol), 2-bromo-5-chloro-pyridine-3-thiol (710 mg, 3.16 mmol) and K2CO3 (729 mg, 5.27 mmol) in DMF (10 mL) was stirred at room temperature for 3 h and then at 50 °C for 2 h. The mixture was diluted with EtOAc and washed with water, NaOH (1 M) and brine. The organic phase was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (700 mg, 60% purity). ESI-MS m / z calculated [C 20 H 21 BrClIN3O7S] [M+H] + : 687.9;Actual value: 687.7.

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[0218] 2-Bromo-5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 2-bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside (700 mg, 60% purity, 1.0 mmol), Pd(dppf)Cl2 (112 mg, 0.152 mmol), (3,4,5-trifluorophenyl)boronic acid (215 mg, 1.22 mmol) and K2CO3 (702 mg, 5.08 mmol) in dioxane (6 mL) and water (3 mL) was stirred at 60° C. for 80 min, followed by stirring at room temperature for 16 h. The mixture was concentrated and partitioned between EtOAc and water. The organic phase was washed with water and brine, dried and concentrated. The residue was purified by chromatography (SiO2, PE / EtOAc) and the resulting material was dissolved in MeOH (20 mL) and NaOMe (2 mL, 1M). After 1 h at room temperature, the reaction was quenched with acetic acid (200 μL) and the mixture was concentrated. The residue was partitioned between EtOAc and water. The organic phase was washed with brine, dried and concentrated. Prep HPLC (C 18 , HO / MeCN / 0.1% TFA) to give the product (60 mg, 9%). ESI-MS m / z calculated [C 20 H 17 BrClF3N3O4S] [M+H] + :566.0;Actual value:565.8.

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[0219] Intermediate 13 2-Bromo-5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside [ka] To a solution of 2,4,6-tri-O-acetyl-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-β-D-galactopyranosyl chloride (270 mg, 0.52 mmol), 2-bromo-5-chloro-pyridine-3-thiol (291 mg, 1.30 mmol) in DMF (5 mL) was added Cs2CO3 (844 mg, 2.59 mmol). After stirring at 40° C. for 18 h, additional 2-bromo-5-chloro-pyridine-3-thiol (100 mg, 0.45 mmol) was added. After 6 h at 50° C., the mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried, concentrated onto silica and purified by chromatography (SiO2, PE / EtOAc). Prep HPLC (C 18 , HO / MeCN / 0.1% TFA) to give the product (51 mg, 17%) as a white solid. ESI-MS m / z calculated [C 20 H 17 BrCl2F2N3O4S] [M+H] + :581.9;Actual value:581.8.

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[0220] Intermediate 14 3-Fluoro-5-methyl-pyridine-2-carbonitrile [ka] A nitrogen purged solution of 2-bromo-3-fluoro-5-methyl-pyridine (300 mg, 1.58 mmol), zinc cyanide (371 mg, 3.16 mmol), 1,1'-bis(diphenylphosphino)ferrocene (71 mg, 0.13 mmol), tris(dibenzylideneacetone)dipalladium(0) (72.6 mg, 0.13 mmol) and Zn (51 mg, 0.79 mmol) in DMF (5 mL) was stirred at 100 °C for 16 h. The mixture was removed from stirring and the solids were allowed to settle. The supernatant was partitioned between EtOAc and brine. The organic phase was washed with brine, dried, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (202 mg, 94%).

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[0221] 5-Chloro-2-methylpyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside [ka] To a solution of 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranosyl chloride (420 mg, 60% purity, 0.84 mmol) in DMF (4 mL) was added potassium thioacetate (144 mg, 1.26 mmol). After stirring at room temperature for 19 h, the mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc). The resulting material was dissolved in DMF (2 mL) together with 3-fluoro-5-methyl-pyridine-2-carbonitrile (90.7 mg, 0.67 mmol) and diethylamine (114 μl, 1.11 mmol) was added. After 20 h at room temperature, the mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (200 mg, 50% purity, 59%). ESI-MS m / z calculated [C 22 H 20 F3N4O4S] [M+H] + : 615.0;Actual value: 614.8.

[0222] Intermediate 15 5-Bromo-2-cyanopyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A nitrogen-purged solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside (2.70 g, 5.15 mmol), K2CO3 (3.56 g, 25.8 mmol), (3,4,5-trifluorophenyl)boronic acid (1.36 g, 7.73 mmol) and Pd(dppf)Cl2 (565 mg, 0.77 mmol) in water / dioxane (1:2, 22.5 mL) was heated at 60° C. for 1 h. The mixture was partitioned between EtOAc and water, the organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc). The obtained material and PCl5 (1.17 g, 5.63 mmol) were dissolved in DCM (45 mL) and BF3OEt2 (0.80 mL, 6.50 mmol) was added. The mixture was stirred at room temperature for 5 h, then diluted with DCM, washed with water and saturated aqueous NaHCO3, dried and evaporated. The residue was dissolved in potassium thioacetate (742 mg, 6.50 mmol) in DMF (20 mL) and the mixture was stirred at 30 °C for 18 h. The mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc). The obtained material and 5-bromo-3-fluoropyridine-2-carbonitrile (750 mg, 3.73 mmol) were dissolved in DMF (8 mL), diethylamine (0.72 mL, 7.00 mmol) was added and the mixture was stirred at room temperature for 2 h. The mixture was partitioned between water and EtOAc and the organic phase was washed with water, dried and evaporated. The residue was further purified by chromatography (SiO2, PE / EtOAc) to give the product (453 mg, 13%). ESI-MS m / z calculated [C 27 H 22 BrF3N4O7S][M+H] + : 683.0;Actual value: 683.0.

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[0223] Intermediate 17 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (428 mg, 0.76 mmol), Pd(dppf)Cl2 (56 mg, 0.076 mmol), bis(pinacolato)diboron (579 mg, 2.28 mmol) and potassium acetate (373 mg, 3.80 mmol) were weighed into a vial and flushed with argon. Degassed DMSO (7.0 mL) was added to the vial and the mixture was stirred at 85 °C for 17 h. The mixture was diluted with EtOAc (100 mL) and washed with water (3 x 100 mL) and brine (100 mL). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (228 mg, 34%). ESI-MS m / z calculated [C 26 H 33 BClN3O9S] [M+H] + :610.2;Actual value:610.0.

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[0224] Intermediate 18 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranosyl chloride (3.0 g, 60% purity, 3.59 mmol), 5-chloropyridine-3-thiol (1.05 g, 7.2 mmol) and Cs2CO3 (2.4 g, 7.2 mmol) in DMF (10.0 mL) was stirred at room temperature for 3 h. The mixture was partitioned between EtOAc and brine, and the organic phase was dried and evaporated. The residue was purified by chromatography (SiO2, PE / EtOAc) to give the product (1.48 g, 75% purity, 26%). ESI-MS m / z calculated [C 20 H 21 ClIN3O7S] [M+H] + :610.0;Actual value:609.8.

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[0225] Intermediate 28 1,2,4,6-Tetra-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-β-D-galactopyranoside [ka] 1,2,4,6-Tetra-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside (5.243 g, 10.0 mmol), Pd(dppf)Cl2 (732 mg, 1.00 mmol), bis(pinacolato)diboron (7.618 g, 30.0 mmol) and potassium acetate (4.907 g, 50.0 mmol) were dissolved in degassed DMF (100 mL) and the mixture was stirred at 60° C. for 2 h. The mixture was filtered through celite, concentrated to about 50 mL and diluted with PE / EtOAc (1:1, 500 mL). The solution was washed with water (3×500 mL) and brine (300 mL). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (4.22 g, 50% purity, 81%). ESI-MS m / z calculated [C 23 H 33 BN2O 11 ] [M+H] + :525.2;Actual value:525.0.

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[0226] 2,4,6-Tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranosyl chloride [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-β-D-galactopyranoside (1.00 g, 50% purity, 1.19 mmol) and PCl5 (794 mg, 3.81 mmol) in DCM (15.7 mL) was added BF3OEt2 (0.47 mL, 3.81 mmol). The mixture was stirred at room temperature for 24 h, then poured into ice / DCM (1:1, 70 mL) and neutralized with NaOH (1 M). The organic phase was separated and the aqueous phase was extracted with DCM (2 x 50 mL). The combined organic phases were washed with brine, dried and evaporated to give the product (1.01 g, 50% purity) which was used in the subsequent step without purification.

[0227] 5-Bromopyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranosyl chloride (500 mg, 50% purity, 1.00 mmol) and 5-bromopyridine-3-thiol (285 mg, 1.50 mmol) in DMF (8.1 mL) was added NaH (60% in oil, 76.5 mg, 2.00 mmol) and the mixture was stirred at room temperature for 21 h. The mixture was diluted with EtOAc (100 mL) and washed with water (5×100 mL) and brine (100 mL). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (189 mg, 20% purity, 29%). ESI-MS m / z calculated value [C 26 H 33 BBrNO9S] [M+H] +: 654.1;Actual value: 654.0.

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[0228] Intermediate 29 5-Chloro-2-cyanophenyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-β-D-galactopyranoside (4.22 g, 50% purity, 8.05 mmol) and PCl5 (3.35 g, 16.1 mmol) in DCM (66.2 mL) was added BF3OEt2 (1.99 mL, 16.1 mmol). The mixture was stirred at room temperature for 1.5 h, then poured onto ice and neutralized with NaOH (1 M). The organic phase was separated and the aqueous phase was extracted with DCM (70 mL). The combined organic phase was dried and evaporated. The residue was dissolved in DMF (25 mL) and 4-chloro-2-sulfanyl-benzonitrile (500 mg, 2.95 mmol) was added followed by NaH (60% in oil, 130 mg, 3.40 mmol) and the mixture was heated at 60° C. for 1 h. EtOAc (250 mL) was added and the mixture was washed with NaOH (0.1 M, 250 mL), water (3×250 mL) and brine (250 mL). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (92 mg, 50% pure, 2%). ESI-MS m / z calculated [C 28 H 33 BClN3O9S] [M+H] + : 634.2;Actual value: 634.0.

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[0229] Intermediate 30 2-Bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranosyl chloride (500 mg, 50% purity, 1.00 mmol) and 2-bromo-5-chloropyridine-3-thiol (336 mg, 1.50 mmol) in DMF (8.1 mL) was added NaH (60% in oil, 76.5 mg, 2.00 mmol) and the mixture was heated at 50° C. for 3 h. The mixture was diluted with EtOAc (100 mL) and washed with water (5×100 mL) and brine (100 mL). The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (53 mg, 50% purity, 8%). ESI-MS m / z calculated value [C 26 H 32 BBrClN3O9S] [M+H] + : 688.1;Actual value: 688.0.

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[0230] 5-Chloro-2-cyanopyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 2-bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (53 mg, 0.077 mmol), zinc cyanide (9.0 mg, 0.077 mmol), Zn (2.5 mg, 0.038 mmol), tris(dibenzylideneacetone)dipalladium(0) (2.8 mg, 0.0031 mmol) and 1,1'-bis(diphenylphosphino)ferrocene (3.5 mg, 0.0062 mmol) in argon-purged DMF (1.0 mL) was stirred at 100 °C for 3 h. Additional zinc cyanide (4.5 mg, 0.038 mmol) was added and the mixture was stirred at 100° C. for 2 h. The mixture was diluted with EtOAc (10 mL), filtered through a plug of celite, and washed with water (5×10 mL) and brine (10 mL). The organic phase was dried, concentrated, and purified by chromatography (SiO2, PE / EtOAc) to give the product (23 mg, 40% pure, 47%). ESI-MS m / z calculated [C 27 H 32 BClN4O9S] [M+H] + : 635.2;Actual value: 634.9.

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[0231] Intermediate 31 2-Benzyloxy-4-bromothiazole [ka] Benzyl alcohol (2.00 g, 18.3 mmol) and NaH (60% in oil, 1.1 g, 27.5 mmol) were weighed into a bottle and THF (10 mL) was added. Once gas evolution had ceased, 2,4-dibromothiazole (3.25 g, 13.0 mmol) was added and the mixture was stirred at room temperature for 1 h. The mixture was partitioned between diethyl ether and water. The organic phase was washed with brine, dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (3.23 g, 92%).

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[0232] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(2-benzyloxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] 5-Chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (100 mg, 0.16 mmol), tetrakis(triphenylphosphine)palladium(0) (19 mg, 0.016 mmol) and 2-benzyloxy-4-bromothiazole (133 mg, 0.49 mmol) were dissolved in a degassed mixture of toluene (1.0 mL), EtOH (0.2 mL) and aqueous Na2CO3 (246 μL, 2 M) and the resulting mixture was refluxed for 2 h. The mixture was cooled to room temperature and the organic phase was separated. The aqueous phase was extracted with EtOAc (2×1 mL) and the combined organic phase was dried and concentrated. The residue was purified by chromatography (SiO2, PE / EtOAc) to give the product (77 mg, 70%). ESI-MS m / z calculated [C 30 H 29 ClN4O8S2] [M+H] + : 673.1;Actual value: 673.2.

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[0233] Intermediate 35 2-Bromo-5-chloropyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside [ka] A solution of 2-bromo-5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (511 mg, 0.90 mmol), benzaldehyde dimethyl acetal (176 μL, 1.17 mmol) and methanesulfonic acid (67 μL, 1.03 mmol) was stirred at room temperature for 30 min, after which Et3N (200 μL) was added. The mixture was diluted with EtOAc (50 mL), washed with water (50 mL) and brine (50 mL), dried and concentrated. The residue was purified by chromatography (SiO2, PE / EtOAc) to give the product (158 mg, 27%). ESI-MS m / z calculated [C 27 H 20 BrClF3N3O4S] [M+H] + : 654.0;Actual value: 653.8.

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[0234] 2-Bromo-5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 2-bromo-5-chloropyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside (158 mg, 0.24 mmol) in DMF (2.0 mL) was added NaH (60% in oil, 19 mg, 0.48 mmol) and iodomethane (22.5 μL, 0.36 mmol) and the mixture was stirred at room temperature for 30 min. The mixture was diluted with EtOAc (10 mL), washed with water (5×10 mL) and brine (10 mL), dried and concentrated. The residue was stirred in 80% aqueous TFA solution (0.83 mL) at room temperature for 20 min. NaOH (10 mL, 1 M) was added and the mixture was extracted with EtOAc (2×10 mL). The combined organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (124 mg, 84%). ESI-MS m / z calculated [C 21 H 18 BrClF3N3O4S] [M+H] + :580.0;Actual value:579.7.

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[0235] Intermediate 36 N-[p-Tolylsulfonyl-(3,4,5-trifluorophenyl)methyl]formamide [ka] To a solution of p-toluenesulfinic acid sodium salt (250 mg, 1.41 mmol) in water (1.67 mL) and tert-butyl methyl ether (0.83 mL) was added concentrated HCl (125 μL) dropwise and the mixture was stirred at room temperature for 10 min. The mixture was diluted and the phases were separated. The organic phase was washed with brine, dried and evaporated. The resulting material was dissolved with 3,4,5-trifluorobenzaldehyde (150 mg, 0.94 mmol), D(+)-10-camphorsulfonic acid (22 mg, 0.094 mmol) and formamide (93 μL, 2.34 mmol) in toluene / MeCN (2.0 mL, 1:1). After stirring at 60° C. for 18 h, the mixture was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (54 mg, 17%). ESI-MS m / z calculated [C 15 H 12 F3NO3S] [M+Na] + :366.0;Actual:366.0.

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[0236] 5-Chloropyridin-3-yl 3-amino-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (330 mg, 0.72 mmol) in MeOH (2 mL) and NaOMe (0.5 mL, 1 M) was stirred at room temperature for 3 h. The mixture was quenched with acetic acid (0.1 mL), concentrated, and partitioned between EtOAc and water. The organic phase was dried, evaporated, and dissolved in MeOH (7 mL). 1,3-Propanedithiol (216 μL, 2.16 mmol) was added followed by Et3N (301 μL, 2.16 mmol) and the mixture was stirred at room temperature for 18 h. The mixture was concentrated and partitioned between EtOAc and water. The aqueous phase was evaporated to give the product (169 mg, 77%). ESI-MS m / z calculated [C11 H 15 ClN2O4S] [M+H] + : 307.0;Actual value: 307.0.

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[0237] Intermediate 37 2-Bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-β-D-galactopyranosyl chloride (798 mg, 1.58 mmol), 2-bromo-5-chloropyridine-3-thiol (474 ​​mg, 1.90 mmol) and K2CO3 (445 mg, 3.2 mmol) in DMF (4.0 mL) was stirred at room temperature for 19 h. The mixture was partitioned between EtOAc and water. The organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (234 mg, 23%).

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[0238] 5-Chloro-2-{N-(2-oxa)-6-azaspiro[3.3]heptanyl}-pyridin-3-yl 3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside [ka] A solution of 2-bromo-5-chloropyridin-3-yl 2,4,6-tri-O-acetyl-3-(4-bromo-1H-1,2-pyrazol-1-yl)-3-deoxy-1-thio-α-D-galactopyranoside (100 mg, 0.15 mmol), DIPEA (0.29 mL, 2.25 mmol) and 2-oxa-6-azaspiro[3.3]heptane oxalate (73 mg, 0.5 mmol) in MeCN (2.0 mL) was stirred in a microwave reactor at 130° C. for 3 h. The mixture was partitioned between EtOAc and water, and the organic phase was dried and evaporated. The resulting material was stirred in MeOH (2.0 mL) and NaOMe (1.0 mL, 1 M) at room temperature for 4 h. The mixture was neutralized with acetic acid (0.2 mL), concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1%TFA) to give the product (42 mg, 43%). ESI-MS m / z calculated [C 19 H 22 BrClN4O5S] [M+H] + :533.0;Actual:533.0.

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[0239] Intermediate 38 3-Deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose [ka] A solution of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (5.00 g, 19.2 mmol) in DCM (100 mL) and pyridine (3.11 mL, 38.4 mmol) was cooled to 0 °C and trifluoromethanesulfonic anhydride (3.88 mL, 23.1 mmol) in DCM (15 mL) was added dropwise. After stirring for 30 min at 10 °C, the mixture was quenched by adding HCl (1 M) dropwise. The mixture was partitioned between DCM and HCl (1 M) and the organic phase was washed with saturated aqueous NaHCO3, dried and concentrated. A portion of the obtained material (2.3 g, 5.86 mmol) and Cs2CO3 (1.91 g, 5.86 mmol) were dissolved in DMF (30 mL). To this solution was added 3-iodopyrazole (1.31 g, 6.74 mmol) and the mixture was stirred at room temperature for 20 h. Ice was added and the solid was filtered off. The solid was purified by chromatography (SiO2, PE / EtOAc) to give the product (1.22 g, 48%). ESI-MS m / z calculated [C 15 H 21 IN2O5] [M+H] + : 437.1;Actual value: 437.0.

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[0240] 1,2,4,6-Tetra-O-acetyl-3-deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside [ka] A solution of 3-deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose (1.22 g, 2.79 mmol) in TFA / water (5 mL, 4:1) was stirred at room temperature for 1 h. Water (2 mL) was added and the mixture was evaporated using MeCN to azeotropically remove water and TFA. Finally, the residue was worked up in vacuum. The crude product was dissolved in EtOAc (8 mL) and Et3N (4.57 mL, 33.5 mmol) was added followed by acetic anhydride (2.64 mL, 27.9 mmol). The mixture was stirred at 30° C. for 16 h. The mixture was cooled to 0° C. and EtOAc (15 mL) was added slowly followed by HCl (30 mL, 1 M). The mixture was stirred for 20 min and then filtered through celite. The organic phase was separated, washed with saturated aqueous NaHCO3 and brine, dried and evaporated. The residue was purified by chromatography (SiO2, PE / EtOAc) to give the product (1.135 g) as a furanoside / pyranoside mixture. This mixture was used in the next step without further purification. ESI-MS m / z calculated [C 17 H 21 IN2O9] [M+H] + :525.0;Actual:525.0.

[0241] 5-Chloropyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside [ka] To a solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranoside (1.10 g, 2.10 mmol) and PCl5 (568 mg, 2.73 mmol) in DCM (20 mL) was added boron trifluoride diethyl etherate (0.78 mL, 6.29 mmol) and the mixture was stirred at room temperature for 7 h. The solution was diluted with DCM and washed with ice / water and saturated aqueous NaHCO3. The organic phase was dried, evaporated and the residue was dissolved in DMF (10 mL) together with 5-chloropyridine-3-thiol (458 mg, 3.15 mmol). K2CO3 (580 mg, 4.20 mmol) was added and the mixture was stirred at room temperature for 16 h. The mixture was diluted with EtOAc and washed twice with water and once with brine. The organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in MeOH (15 mL) and NaOMe (1 mL, 1M) at room temperature for 1 h. The reaction was quenched with dowex, filtered and the filtrate was evaporated. The resulting residue and p-toluenesulfonic acid monohydrate (58 mg, 0.30 mmol) were dissolved in MeCN (40 mL) and benzaldehyde dimethyl acetal (0.23 mL, 1.51 mmol) were added. After the mixture was stirred at room temperature for 3 days, more p-toluenesulfonic acid monohydrate (58 mg, 0.30 mmol) and benzaldehyde dimethyl acetal (0.23 mL, 1.51 mmol) were added and the mixture was stirred at room temperature for another 20 h. Et3N (0.14 mL, 1.01 mmol) was added and the mixture was concentrated. The residue was partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (226 mg, 19% yield). ESI-MS m / z calculated [C 21 H 19 ClIN3O4S] [M+H] + :572.0;Actual:572.0.

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[0242] 5-Chloropyridin-3-yl 3-deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 5-chloropyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-(3-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside (226 mg, 0.40 mmol) in DMF (5 mL) was added NaH (60% in oil, 30 mg, 0.79 mmol) followed by iodomethane (37 μL, 0.59 mmol) and the mixture was stirred at room temperature for 1 h. The mixture was diluted with EtOAc, washed twice with water, the organic phase was dried and evaporated. The residue was stirred at 80 °C in acetic acid / water (5 mL, 9:1) for 3 h. The mixture was partitioned between EtOAc and water and the organic phase was washed with saturated aqueous NaHCO3, dried and evaporated. The residue was stirred in NaOMe (0.1 mL, 1 M) and MeOH (1.5 mL) for 1 h at room temperature. The mixture was concentrated and purified by Prep HPLC (C 18 , H2O / MeCN / 0.1% TFA) to give the product (145 mg, 74%). ESI-MS m / z calculated [C 15 H 17 ClIN3O4S] [M+H] + :498.0;Actual:498.0.

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[0243] Intermediate 39 2-Bromo-1-(3,4,5-trifluorophenyl)ethanone [ka] To a solution of 1-(3,4,5-trifluorophenyl)ethanone (960 mg, 5.51 mmol) in DCM (50 mL) was added tert-butyldimethylsilyl trifluoromethanesulfonate (2.186 g, 8.27 mmol) and Et3N 1.12 g, 11.0 mmol) and the mixture was stirred at room temperature for 1 h. The mixture was partitioned between DCM (50 mL) and aqueous NaHCO3 (60 mL). The organic phase was dried over Na2SO4 and concentrated. The residue was dissolved in THF (50 mL) and N-bromosuccinimide (981 mg, 5.51 mmol) and water (993 mg) were added. The mixture was stirred at room temperature for 15 min before diethyl ether (100 mL) was added. The mixture was washed with water (80 mL), aqueous NaHCO3 (60 mL) and brine (80 mL). The organic phase was dried over MgSO4, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (800 mg, 57%).

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[0244] Methyl 3-O-allyl-α-D-galactopyranoside [ka] To a solution of methyl α-D-galactopyranoside (19.4 g, 100 mmol) in anhydrous methanol (200 mL) was added dibutyltin oxide (27.4 g, 110 mmol) and the mixture was refluxed for 4 h. The mixture was concentrated. The dry residue was suspended in toluene (200 mL) and treated with allyl bromide (14.5 g, 120 mmol) and tetrabutylammonium bromide (32.2 g, 100 mmol). The suspension was stirred at 60° C. for 18 h. The mixture was evaporated and purified by chromatography (SiO2, EtOAc) to give the product (20 g, 85%). ESI-MS m / z calculated [C 10 H 18 O6] [M+NH4] + :252.1;Actual value:252.1.

[0245] Methyl 3-O-allyl-2,4,6-tri-O-benzyl-α-D-galactopyranoside [ka] To a cooled (0° C.) solution of methyl 3-O-allyl-α-D-galactopyranoside (15 g, 64 mmol) in DMF (150 mL) was added NaH (60% in oil, 12.81 g, 320 mmol). After 15 min, benzyl bromide (36.14 g, 0.21 mol) was added and the mixture was stirred at room temperature for 16 h. EtOAc (600 mL) was added and the mixture was washed with HCl (400 mL, 1 M), water (400 mL) and brine. The organic phase was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (27 g, 84%). ESI-MS m / z calculated [C 31 H 36 O6] [M+NH4] + :522.3;Actual value:522.2.

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[0246] Methyl 2,4,6-tri-O-benzyl-α-D-galactopyranoside [ka] To a solution of methyl 3-O-allyl-2,4,6-tri-O-benzyl-α-D-galactopyranoside (23 g, 46 mmol) in MeOH (200 mL) was added palladium(II) chloride (840 mg, 4.73 mmol) and the mixture was stirred at room temperature for 16 h. The mixture was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (21 g, 91%). ESI-MS m / z calculated [C 28 H 32 O6] [M+NH4] + : 482.2;Actual value: 482.2.

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[0247] Methyl 2,4,6-tri-O-benzyl-α-D-xylo-hex-3-ulopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-α-D-galactopyranoside (11 g, 24 mmol) in DCM (120 mL) was added Dess-Martin Periodinane (15.06 g, 40 mmol) and the mixture was stirred at room temperature for 24 h. The mixture was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (10 g, 91%). ESI-MS m / z calculated [C 28 H 30 O6] [M+NH4] + : 480.2;Actual value: 480.2.

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[0248] Methyl 2,4,6-tri-O-benzyl-3-C-cyano-α-D-gulopyranoside [ka] To a cooled (0° C.) solution of methyl 2,4,6-tri-O-benzyl-α-D-xylo-hex-3-ulopyranoside (1.29 g, 2.8 mmol) and trimethylsilyl cyanide (1.29 g, 13.0 mmol) in DCM (20 mL) was added AlCl3 (1.15 g, 8.65 mmol) and the mixture was stirred at room temperature for 3 h. NH4Cl (aq, 100 mL) was added and the mixture was extracted with DCM. The organic phase was dried over Na2SO4, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (1.5 g, 71%). ESI-MS m / z calculated [C 29 H 31 NO6] [M+NH4] + :507.2;Actual value:507.2.

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[0249] Methyl 2,4,6-tri-O-benzyl-3-C-cyano-3-O-phenoxythiocarbonyl-α-D-gulopyranoside [ka] To a cooled (0° C.) solution of methyl 2,4,6-tri-O-benzyl-3-C-cyano-α-D-gulopyranoside (2.05 g, 4.19 mmol), Et3N (424 mg, 4.19 mmol) and 4-(dimethylamino)pyridine (153 mg, 1.26 mmol) in MeCN (25 mL) was added O-phenylchloromethanethioate (1084 mg, 6.28 mmol) and the mixture was stirred at room temperature overnight. The mixture was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (1.7 g, 65%). ESI-MS m / z calculated [C 36 H 35 NO7S] [M+H] + : 626.2;Actual value: 626.2.

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[0250] Methyl 2,4,6-tri-O-benzyl-3-C-cyano-3-deoxy-α-D-galactopyranoside [ka] A solution of methyl 2,4,6-tri-O-benzyl-3-C-cyano-3-O-phenoxythiocarbonyl-α-D-gulopyranoside (1.7 g, 2.72 mmol), tris(trimethylsilyl)silane (1351 mg, 5.43 mmol) and 2,2'-azobis(2-methylpropionitrile (446 mg, 2.72 mmol) in toluene (10 mL) was stirred at 100 °C under nitrogen for 2 h. The mixture was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (610 mg, 47%). ESI-MS m / z calculated [C 29 H 31 NO5] [M+NH4] + : 491.2;Actual value: 491.3.

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[0251] Methyl 2,4,6-tri-O-benzyl-3-C-carbamoyl-3-deoxy-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-C-cyano-3-deoxy-α-D-galactopyranoside (630 mg, 1.33 mmol) in DMSO (25 mL) was added K2CO3 (96 mg, 0.7 mmol) and the mixture was cooled to 0° C. Hydrogen peroxide (4 mL, 30 wt % in H2O) was added and the mixture was stirred at 30° C. for 1 h. The mixture was poured into water (150 mL) and the precipitate was collected and dissolved in EtOAc (100 mL). The mixture was washed with brine (80 mL), dried over Na2SO4 and concentrated to give the product (500 mg, 77%). ESI-MS m / z calculated [C 29 H 33 NO6] [M+H] + : 492.2;Actual value: 492.2.

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[0252] Methyl 2,4,6-tri-O-benzyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-C-carbamoyl-3-deoxy-α-D-galactopyranoside (110 mg, 0.22 mmol) in EtOAc (25 mL) was added silver trifluoromethanesulfonate (115 mg, 0.45 mmol) and 2-bromo-1-(3,4,5-trifluorophenyl)ethanone (113 mg, 0.45 mmol) and the mixture was stirred at 60° C. in the dark for 16 h. The mixture was concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (60 mg, 42%). ESI-MS m / z calculated [C 37 H 34 F3NO6] [M+H] + : 646.2;Actual value: 646.2.

[0253] Methyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-α-D-galactopyranoside (1.00 g, 1.55 mmol) in MeOH (50 mL), Pd / C (5% Pd, 200 mg) was added and stirred at room temperature under H2 pressure for 48 h. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in pyridine (5 mL) and acetic anhydride (2 mL) was added. The mixture was stirred at room temperature overnight. The mixture was poured into water (100 mL) and extracted with EtOAc (2 x 100 mL). The organic layer was washed with water (50 mL), HCl (50 mL, 1 M) and brine (50 mL), dried over Na2SO4, concentrated and purified by column chromatography (PE / EA=10 / 1 to 1 / 1, Silica-CS4g, 10 mL / min, silica gel, UV254) to give the product (590 mg, 76%). ESI-MS m / z calculated [C 22 H 22 F3NO9] [M+H] + :502.1;Actual value:502.2.

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[0254] Acetyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-α-D-galactopyranoside (560 mg, 1.12 mmol) in acetic anhydride (4 mL) and acetic acid (2 mL), H2SO4 (98.0%, 112 mg, 1.12 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (2 x 100 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried over Na2SO4, concentrated and purified by column chromatography (PE / EA = 10 / 1 to 1 / 1, Silica-CS12 g, 20 mL / min, silica gel, UV254) to give the product (400 mg, 68%). ESI-MS m / z calculated [C 23 H 22 F3NO 10 ] [M+H] + :530.1;Actual value:530.2.

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[0255] 3,4-Dichlorophenyl 2,4-di-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of acetyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-α-D-galactopyranoside (110 mg, 0.21 mmol) in 1,2-dichloroethane (10.0 mL) was added 3,4-dichlorobenzenethiol (446 mg, 2.49 mmol) and boron trifluoride diethyl etherate (0.256 mL, 2.08 mmol) and the mixture was stirred for 16 h at 55° C. The mixture was poured into water (50 mL) and extracted with EtOAc (2×50 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA=10 / 1 to 1 / 1, Silica-CS4g, 10 mL / min, silica gel, UV254) to give the product (40.0 mg, 32%). ESI-MS m / z calculated [C 25 H 20 Cl2F3NO7S][M+H] + :606.0;Actual value:606.0.

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[0256] Intermediate 40 Methyl 2,4,6-tri-O-benzyl-3-C-carbamothioyl-3-deoxy-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-C-carbamoyl-3-deoxy-α-D-galactopyranoside (1.00 g, 2.03 mmol) in THF (20.0 mL), Lawesson's reagent (823 mg, 2.03 mmol) was added and the mixture was stirred under reflux for 2 h. The mixture was concentrated and purified by reverse phase chromatography (MeCN / HO=1 / 20 to 3 / 1, C-18 column, 20 mL / min, UV254) to give the product (600 mg, 58%). ESI-MS m / z calculated [C 29 H 33 NO5S] [M+H] +:508.2;Actual value:508.2.

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[0257] Methyl 2,4,6-tri-O-benzyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-C-carbamothioyl-3-deoxy-α-D-galactopyranoside (600 mg, 1.18 mmol) in EtOH (20.0 mL), 2-bromo-1-(3,4,5-trifluorophenyl)ethanone (598 mg, 2.36 mmol) was added and the mixture was refluxed for 2 h. The mixture was concentrated and purified by column chromatography (PE / EA=10 / 1 to 5 / 1, Silica-CS20 g, 20 mL / min, silica gel, UV254) to give the product (670 mg, 86%). ESI-MS m / z calculated [C 37 H 34 F3NO5S] [M+H] + : 662.2;Actual value: 662.2.

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[0258] Methyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-α-D-galactopyranoside (450 mg, 0.68 mmol) in DCM (25 mL) was added trichloroborane (1 M in DCM, 10.2 mL) at -70°C. The mixture was allowed to warm slowly to room temperature. After 2 h, MeOH (5 mL) was added and the mixture was concentrated. The residue was dissolved in pyridine (3 mL), acetic anhydride (1.5 mL) was added and the mixture was stirred at room temperature overnight. The mixture was poured into water (100 mL) and extracted with EtOAc (2 x 100 mL). The organic layer was washed with water (50 mL), HCl (1M, 50 mL), brine (50 mL), dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA=10 / 1 to 1 / 1, Silica-CS4g, 10 mL / min, silica gel, UV254) to give the product (160 mg, 46%). ESI-MS m / z calculated [C 22 H 22 F3NO8S] [M+H] + :518.1;Actual value:518.2.

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[0259] Acetyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-α-D-galactopyranoside (160 mg, 0.31 mmol) in acetic anhydride (3 mL) and acetic acid (1 mL) was added H2SO4 (98.0%, 61.8 mg, 0.62 mmol) and the mixture was stirred at room temperature overnight. The mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (2 x 100 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried over Na2SO4, concentrated and purified by column chromatography (PE / EA = 10 / 1 to 1 / 1, Silica-CS12 g, 20 mL / min, silica gel, UV254) to give the product (100 mg, 59%). ESI-MS m / z calculated [C 23 H 22 F3NO9S] [M+H] + :546.1;Actual value:546.1.

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[0260] 3,4-Dichlorophenyl 2,4-di-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-1-thio-α-D-galactopyranoside [ka] To a solution of acetyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-α-D-galactopyranoside (100 mg, 0.18 mmol) in 1,2-dichloroethane (10.0 mL) was added 3,4-dichlorobenzenethiol (263 mg, 1.47 mmol) and boron trifluoride diethyl etherate (0.226 mL, 1.83 mmol) and the mixture was stirred for 16 h at 55° C. The mixture was poured into water (50 mL) and extracted with EtOAc (2×50 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA=10 / 1 to 1 / 1, Silica-CS4g, 10 mL / min, silica gel, UV254) to give the product (20 mg, 12%). ESI-MS m / z calculated [C 25 H 20 Cl2F3NO6S2] [M+H] + :622.0;Actual value:622.0.

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[0261] Intermediate 41 Methyl 2,4,6-tri-O-benzyl-3-C-carboxy-3-deoxy-α-D-galactopyranoside [ka] To a cooled (0°C) solution of methyl 2,4,6-tri-O-benzyl-3-C-carbamoyl-3-deoxy-α-D-galactopyranoside (1.20 g, 2.44 mmol) in dioxane (18 mL) was added concentrated hydrochloric acid (2.03 mL, 2.44 mmol) dropwise, followed by the portionwise addition of solid sodium nitrite (1.68 g, 2.44 mmol). The mixture was stirred at room temperature for 3 h, then poured into ice / water (30 mL) and extracted with DCM (2 x 20 mL). The combined organic layers were dried over MgSO4 and evaporated to give the product (1.10 g, 92%). ESI-MS m / z calculated [C 29 H 32O7] [M+NH4] + :510.2;Actual value:510.4.

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[0262] Methyl 2,4,6-tri-O-benzyl-3-C-[2-(3,4,5-trifluorophenyl)carbohydrazide]-3-deoxy-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-C-carboxy-3-deoxy-α-D-galactopyranoside (1.10 g, 2.23 mmol) in DCM (15 mL) was added HATU (1.02 g, 2.68 mmol), Et3N (1.25 mL, 8.93 mmol) and 3,4,5-trifluorobenzohydrazide (510 mg, 2.68 mmol) and the mixture was stirred at room temperature under nitrogen atmosphere for 3 h. The mixture was poured into water (20 mL) and extracted with DCM (2×20 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried over Na2SO4, concentrated and purified by column chromatography (PE / EA=1 / 1-0 / 1, Silica-CS20 g, 20 mL / min, silica gel, UV254) to give the product (1.04 g, 63%). ESI-MS m / z calculated value [C 36 H 35 F3N2O7] [M+H] + : 665.2;Actual value: 665.3.

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[0263] Methyl 2,4,6-tri-O-benzyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-C-[2-(3,4,5-trifluorophenyl)carbohydrazide]-3-deoxy-α-D-galactopyranoside (1.04 g, 1.56 mmol) in DMF (10 mL) and THF (1 mL) was added Burgess reagent (1.49 g, 6.26 mmol) and the mixture was stirred at 125° C. for 90 min in a microwave reactor. The mixture was concentrated and purified by column chromatography (PE / EA=2:1, Silica-CS 12 g, 20 mL / min, silica gel, UV254) to give the product (610 mg, 60%). ESI-MS m / z calculated [C 36 H 33 F3N2O6] [M+H] + : 647.2;Actual value: 647.3.

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[0264] Methyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-benzyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-α-D-galactopyranoside (610 mg, 0.94 mmol) in MeOH (10 mL) was added Pd / C (5% Pd, 150 mg) and the mixture was stirred at room temperature under H2 pressure for 48 h. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in pyridine (5 mL), acetic anhydride (2 mL) was added and the mixture was stirred at room temperature overnight. The mixture was poured into water (10 mL) and extracted with EtOAc (2 x 100 mL). The organic layer was washed with water (20 mL), HCl (20 mL, 1 M) and brine (20 mL), dried over Na2SO4, concentrated and purified by column chromatography (PE / EA=10 / 1 to 1 / 1, Silica-CS4g, 10 mL / min, silica gel, UV254) to give the product (320 mg, 68%). ESI-MS m / z calculated [C 21 H 21 F3N2O9][M+NH4] + :520.1;Actual value:520.1.

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[0265] Acetyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-α-D-galactopyranoside [ka] To a solution of methyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-α-D-galactopyranoside (320 mg, 0.64 mmol) in acetic anhydride (2.5 mL) and acetic acid (1 mL) was added H2SO4 (98.0%, 63.7 mg, 0.64 mmol) and the mixture was stirred at room temperature overnight. The mixture was poured into saturated aqueous NaHCO3 (30 mL) and extracted with EtOAc (2 x 30 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried over Na2SO4, concentrated and purified by column chromatography (PE / EA=10 / 1-3 / 1, Silica-CS12 g, 20 mL / min, silica gel, UV254) to give the product (230 mg, 68%). ESI-MS m / z calculated value [C 22 H 21 F3N2O 10 ] [M+H] + :531.1;Actual value:531.1.

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[0266] 3,4-Dichlorophenyl 2,4-di-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-1-thio-D-galactopyranoside [ka] To a cooled (0° C.) solution of acetyl 2,4,6-tri-O-acetyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-α-D-galactopyranoside (110 mg, 0.21 mmol) and 3,4-dichlorobenzenethiol (186 mg, 1.04 mmol) in 1,2-dichloroethane (5.0 mL), boron trifluoride diethyl etherate (0.256 mL, 2.07 mmol) was added and the mixture was stirred for 16 h at 50° C. The mixture was poured into water (20 mL) and extracted with EtOAc (2×20 mL). The organic layer was washed with water (20 mL), brine (20 mL), dried over Na2SO4, concentrated, and purified by column chromatography (PE / EA=10 / 1 to 1 / 1, Silica-CS4g, 10 mL / min, silica gel, UV254) to give the product (19 mg, 15%). ESI-MS m / z calculated [C 24 H 19 Cl2F3N2O7S] [M+H] + :607.0;Actual value:607.0.

[0267] Intermediate 42 2-(2-benzyloxythiazol-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ka] 2-Benzyloxy-4-bromothiazole (1.00 g, 3.7 mmol), potassium acetate (1.1 g, 11.1 mmol) and bis(pinacolato)diboron (1.92 g, 7.4 mmol) were suspended in dioxane (10 mL), degassed with nitrogen and (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (156 mg, 0.19 mmol) and potassium tert-butoxide (21 mg, 0.19 mmol) were added. The mixture was stirred at 80°C for 10 h and then partitioned between EtOAc and brine. The organic phase was dried, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (1.00 g, 85%).

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[0268] 3,4-Dichlorophenyl 3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranosyl chloride (3.17 g, 4.00 mmol), 3,4-dichlorobenzenethiol (0.64 mL, 4.8 mmol) and Cs2CO3 (1.63 g, 5.00 mmol) in DMF (25 mL) was stirred at room temperature for 20 h. The mixture was partitioned between EtOAc and brine, the organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc). The resulting material was stirred in MeOH (30 mL) and NaOMe (2.0 mL, 1 M) at room temperature for 3 h. The mixture was neutralized with dowex, filtered, evaporated and purified by chromatography (SiO2, PE / EtOAc) to give the product (1.31 g, 63%). ESI-MS m / z calculated [C 15 H 15Cl2IN2O4S] [M+H] + :516.9;Actual value:516.9.

number

[0269] 3,4-Dichlorophenyl 3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-2-O-methyl-1-thio-α-D-galactopyranoside [ka] To a solution of 3,4-dichlorophenyl 3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside (1.313 g, 2.5 mmol) in MeCN (30 mL) was added benzaldehyde dimethyl acetal (0.57 mL, 3.75 mmol) and p-toluenesulfonic acid monohydrate (50 mg, 0.26 mmol) and the mixture was stirred at room temperature for 1 h. Et3N (0.5 mL) was added, followed by water (5 mL) and the mixture was stirred at room temperature for 15 min. The precipitate formed was isolated by filtration, washed with PE, then with 33% aqueous MeOH and dried. The resulting material was dissolved in DMF (10 mL) and NaH (60% in oil, 155 mg, 3.86 mmol) was added, followed by iodomethane (0.24 mL, 3.86 mmol). After stirring at room temperature for 1 h, MeOH (20 mL) and water (5 mL) were added. The precipitate was isolated by filtration, washed with 50% aqueous MeOH, and dried. The resulting material was stirred in 80% aqueous TFA (15 mL) at room temperature for 30 min, then partitioned between EtOAc and water. The organic phase was washed with NaOH (5 M, 40 mL), dried, and evaporated to give a white solid, which was triturated in PE to give the product (828 mg, 61%). ESI-MS m / z calculated [C 16 H 17 Cl2IN2O4S] [M+H] + :530.9;Actual value:530.9.

number

[0270] Intermediate 43 tert-Butyl N-(4-bromothiazol-2-yl)carbamate [ka] An argon-degassed solution of 2,4-dibromothiazole (972 mg, 4.00 mmol), tert-butyl carbamate (515 mg, 4.40 mmol), tris(dibenzylideneacetone)dipalladium(0) (69 mg, 0.12 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (93 mg, 0.16 mmol) and Cs2CO3 (2.61 g, 8.00 mmol) in dioxane (13 mL) was stirred at 85 °C for 24 h. The mixture was cooled to room temperature, filtered through a celite plug and concentrated. The residue was purified by chromatography (SiO2, PE / EtOAc) to give the product (113 mg, 8%).

number

[0271] [2-(tert-butoxycarbonylamino)thiazol-4-yl]boronic acid [ka] To an argon-degassed solution of (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (3.8 mg, 0.0045 mmol) and potassium tert-butoxide (0.5 mg, 0.0045 mmol) in dioxane (0.5 mL) was added tert-butyl N-(4-bromothiazol-2-yl)carbamate (50 mg, 0.15 mmol), potassium acetate (44 mg, 0.45 mmol) and bis(pinacolato)diboron (76 mg, 0.30 mmol) and the mixture was stirred at 80 °C for 19.5 h. Additional (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (1.8 mg, 0.0021 mmol) and potassium tert-butoxide (0.24 mg, 0.0021 mmol) were added and the mixture was stirred at 80°C for 24 h. The mixture was cooled to room temperature, filtered through a celite plug and evaporated. The residue was added to a silica plug, washed with EtOAc and eluted with MeOH / AcOH (20:1) to give the product (20 mg, 55%).

number

[0272] Intermediate 44 5-Chloro-2-cyanophenyl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside [ka] A solution of 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-β-D-galactopyranosyl chloride (2.83 g, 3.56 mmol), 4-chloro-2-sulfanylbenzonitrile (950 mg, 3.92 mmol) and Cs2CO3 (1.74 g, 5.34 mmol) in DMF (9.0 mL) was stirred at room temperature for 16 h. The mixture was partitioned between EtOAc and brine, and the organic phase was dried, concentrated and purified by chromatography (SiO2, PE / EtOAc) to give the product (686 mg, 30%). ESI-MS m / z calculated [C 22 H 21 ClIN3O7S] [M+H] + : 634.0;Actual value: 634.0.

number

[0273] 5-Chloro-2-cyanophenyl 4,6-O-benzylidene-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-2-O-methyl-1-thio-α-D-galactopyranoside [ka] A solution of 5-chloro-2-cyanophenyl 2,4,6-tri-O-acetyl-3-deoxy-3-(4-iodo-1H-1,2-pyrazol-1-yl)-1-thio-α-D-galactopyranoside (686 mg, 1.08 mmol) in MeOH (25 mL) and NaOMe (2.0 mL, 1 M) was stirred at room temperature for 2 h. The mixture was neutralized with dowex, filtered, and evaporated. Water was added, and the precipitate was isolated by filtration, washed with 33% aqueous MeOH, and dried. The resulting material was dissolved in MeCN (8 mL) and benzaldehyde dimethyl acetal (0.17 mL, 1.1 mmol) and p-toluenesulfonic acid monohydrate (50 mg, 0.26 mmol) were added. The mixture was stirred at room temperature for 16 h, after which Et3N (70 μL) was added, followed by water (3 mL). The precipitate that formed was isolated by filtration, washed with 33% aqueous MeOH, and dried. The resulting material was stirred in DMF (2.0 mL) and NaH (60% in oil, 50 mg, 1.25 mmol) was added, followed by iodomethane (60 μL, 0.93 mmol). After stirring at room temperature for 3 h, the mixture was poured onto ice and HCl (1 M). The precipitate was isolated by filtration, washed with 33% aqueous MeOH, dried, and purified by chromatography (SiO2, PE / EtOAc) to give the product (63 mg, 17%). ESI-MS m / z calculated [C 24 H 21 ClIN3O4S] [M+H] + :610.0;Actual value:610.0.

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[0274] References JPEG0007674275000285.jpg215126 JPEG0007674275000286.jpg222126 JPEG0007674275000287.jpg228126 JPEG0007674275000288.jpg226126 JPEG0007674275000289.jpg194126

Claims

1. A D-galactopyranose compound of formula (1): 【Chemistry 1】 During the ceremony, the pyranose ring is α-D-galactopyranose; A １ is R １ -Z, During the ceremony, Z is selected from 1,2,4-triazolyl, oxazolyl, isoxazolyl, oxadiazolyl, dioxolyl, dithiolyl, thiazolyl, isothiazolyl, furanyl, thiophene, pyrrolyl, imidazolyl or pyrazolyl and is attached to an α-D-galactopyranose; R １ a) halogen, CN; -COOH; -CONR ６ａ R ７ａ (R ６ａ and R ７ａ are independently H, C １－３ selected from the group consisting of alkyl, cyclopropyl and isopropyl, or R ６ａ and R ７ａ may form a heterocycloalkyl together with the nitrogen), C optionally substituted with F １－３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F １－３ Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR ８ａ R ９ａ (R ８ａ and R ９ａ are independently H, C １－３ alkyl and isopropyl); OH; and R １０ａ -CONH-(R １０ａ is C １－３ a) aryl, including phenyl or naphthyl, optionally substituted with a group selected from the group consisting of: halogen; spiroheterocycle; CN; -COOH; -CONR １２ａ R １３ａ (R １２ａ and R １３ａ are independently H, C １－３ C optionally substituted with F; １－３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F １－３ Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR １４ａ R １５ａ (R １４ａ and R １５ａ are independently H, C １－３ alkyl, cyclopropyl and isopropyl), C(═O)—R ２１ａ (R ２１ａ is H and C １－３ alkyl); OH; and R １６ａ -CONH-(R １６ａ is C １－３ a heterocycle, including heteroaryl or heterocycloalkyl, optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl; X is S, SO, SO ２ , O, C=O, and CR ２ｂ R ３ｂ R ２ｂ and R ３ｂ is independently selected from hydrogen, OH, or halogen; B １ a) CN, halogen, methyl which may be substituted with F, OCH which may be substituted with F ３ , OCH optionally substituted with F ２ CH ３ , O-H, and R ４ｂ -CONH-(R ４ｂ is C １－３ C substituted with a 5- or 6-membered heteroaromatic ring optionally substituted with a substituent selected from the group consisting of alkyl and cyclopropyl １－６ Alkyl or branched C ３－６ Alkyl; or CN, halogen, methyl optionally substituted with F, OCH optionally substituted with F ３ , OCH optionally substituted with F ２ CH ３ , O-H, and R ５ｂ -CONH-(R ５ｂ is C １－３ phenyl-substituted C, optionally substituted with a substituent selected from the group consisting of alkyl and cyclopropyl; １－６ alkyl, b) halogen; CN; spiroheterocycles including N-(2-oxa)-6-azaspiro[3.3]heptanyl; C ２ -alkynyl; -COOH; -CONR ６ｂ R ７ｂ (R ６ｂ and R ７ｂ are independently H, C １－３ selected from the group consisting of alkyl, cyclopropyl and isopropyl, or R ６ｂ and R ７ｂ may be taken together with the nitrogen to form a heterocycloalkyl; C optionally substituted with F １－３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F １－３ Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR ８ｂ R ９ｂ (R ８ｂ and R ９ｂ is H, C １－３ C optionally substituted with OH; １－３ a heterocycle optionally substituted with alkyl; and R １０ｂ -CONH-(R １０ｂ is C １－３ aryl, including phenyl or naphthyl, optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl; c) halogen, ２ -alkynyl, CN, methyl optionally substituted with F, OCH optionally substituted with F ３ , OCH optionally substituted with F ２ CH ３ , O-H, and R １１ｂ -CONH-(R １１ｂ is C １－３ C, optionally substituted with a substituent selected from the group consisting of alkyl and cyclopropyl ５－７ cycloalkyl, and d) halogen; spiroheterocycles including N-(2-oxa)-6-azaspiro[3.3]heptanyl; ２ -Alkynyl; CN; -COOH; -CONR １２ｂ R １３ｂ (R １２ｂ and R １３ｂ are independently H, C １－３ C optionally substituted with F; １－３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; OC optionally substituted with F １－３ Alkyl; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; NR １４ｂ R １５ｂ (R １４ｂ and R １５ｂ are independently H, C １－３ alkyl and isopropyl; OH; C optionally substituted with OH １－３ a heterocycle optionally substituted with alkyl; and R １６ｂ -CONH-(R １６ｂ is C １－３ e) a heterocycle including heteroaryl or heterocycloalkyl, optionally substituted with a group selected from the group consisting of alkyl and cyclopropyl; １－６ Alkyl or branched C ３－６ Alkyl; f) C ２－６ alkynyl, R ５０ is a) H, b) OH, c) phenyl substituted with one or more groups selected from the group consisting of halogen, phenyl, OH and halogen, CN, OR １７ｂ , N.R. １８ｂ R １９ｂ , and C.O.N.H. ２ OC optionally substituted with one or more of １－６ Alkyl (R １７ｂ is H, CN, halogen, methyl which may be substituted with F, OCH which may be substituted with F ３ , OCH optionally substituted with F ２ CH ３ , O-H, and R ２０ｂ -CONH-, R ２０ｂ is C １－３ R is selected from the group consisting of alkyl and cyclopropyl; １８ｂ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , O-H, and R ２１ｂ -CONH-, R ２１ｂ is C １－３ R is selected from the group consisting of alkyl and cyclopropyl; １９ｂ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , O-H, and R ２２ｂ -CONH-, R ２２ｂ is C １－３ alkyl and cyclopropyl); d) halogen, CN, OR ２３ｂ , N.R. ２４ｂ R ２５ｂ , and C.O.N.H. ２ A branched OC optionally substituted with one or more of ３－６ Alkyl (R ２３ｂ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , OH and R ２６ｂ -CONH-, R ２６ｂ is C １－３ R is selected from the group consisting of alkyl and cyclopropyl; ２４ｂ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , OH and R ２７ｂ -CONH-, R ２７ｂ is C １－３ R is selected from the group consisting of alkyl and cyclopropyl; ２５ｂ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , OH and R ２８ -CONH-, R ２８ is C １－３ alkyl and cyclopropyl; and e) halogen, CN, OR ２９ , N.R. ３０ R ３１ and C.O.N.H. ２ A cyclic OC optionally substituted with one or more of ３－６ Alkyl (R ２９ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , OH and R ３２ -CONH-, R ３２ is C １－３ R is selected from the group consisting of alkyl and cyclopropyl; ３０ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , OH and R ３３ -CONH-, R ３３ is C １－３ is selected from the group consisting of alkyl and cyclopropyl, and R ３１ is H, CN, halogen, methyl optionally substituted with F, OCH ３ , OCH optionally substituted with F ２ CH ３ , OH and R ３４ -CONH-, R ３４ is C １－３ alkyl and cyclopropyl; A D-galactopyranose compound, or a pharma- ceutically acceptable salt or solvate thereof.

2. Z, 【Chemistry 2】 2. The compound of claim 1, wherein the asterisk on the carbon is attached to R1 and the asterisk on the nitrogen is attached to α-D-galactopyranose.

3. R １ CN, OH, NH ２ , F, Br, Cl, I, methyl optionally substituted with fluorine (F), OCH optionally substituted with F ３ and SCH optionally substituted with F ３ The compound according to any one of claims 1 to 2, which is a phenyl optionally substituted with a group selected from the group consisting of:

4. R １ Br; F; Cl; I; OH; CN; NR １４ａ R １５ａ (R １４ａ and R １５ａ are independent and H, C １－３ alkyl, cyclopropyl and isopropyl), C(═O)—R ２１ａ (R ２１ａ H and C １－３ C optionally substituted with F １－３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; OC １－３ alkyl; and SC optionally substituted with F １－３ 3. The compound according to claim 1 or 2, wherein the heteroaromatic ring is selected from the group consisting of 5- or 6-membered heteroaromatic rings, optionally substituted with a group selected from the group consisting of alkyl.

5. R １ But, OH, NH ２ , CN, Br, Cl, I, F, methyl optionally substituted with F, OCH optionally substituted with F ３ and SCH optionally substituted with F ３ Pyridinyl optionally substituted with a group selected from the group consisting of H, CN, Br, Cl, I, F, methyl optionally substituted with F, OCH optionally substituted with F ３ and SCH optionally substituted with F ３ 5. The compound of claim 4, which is pyrimidyl optionally substituted with a group selected from the group consisting of:

6. R １ is a 5- or 6-membered heteroaromatic ring selected from the group consisting of pyrazolyl, imidazolyl, oxazolyl, and formulas 2-9, and the asterisk * indicates the carbon atom of the heteroaromatic ring that is covalently bonded to the Z substituent; 【Chemistry 3】 R ２ ~R ２３ and R ２７ are independently H; halogen; OH; CN; SH; S-C １－３ Alkyl; C optionally substituted with F １－３ Alkyl; cyclopropyl optionally substituted with F; isopropyl optionally substituted with F; O-cyclopropyl optionally substituted with F; O-isopropyl optionally substituted with F; OC １－３ Alkyl; and NR ２４ R ２５ (R ２４ H and C １－３ alkyl; R ２５ H, C １－３ Alkyl and COR ２６ R ２６ H and C １－３ The compound according to any one of claims 1 to 2, wherein the aryl group is selected from the group consisting of alkyl.

7. R １ but, 【Chemistry 4】 is selected from the group consisting of R ２ is selected from the group consisting of OH, methyl and halogens including F, Cl and Br; R ３ is hydrogen, C １－６ selected from the group consisting of alkyl and halogen; R ４ But, OH, NH ２ and halogens, including F, Cl and Br; R ５ is hydrogen, C １－６ 7. The compound of claim 6, wherein the radical is selected from the group consisting of alkyl and halogen.

8. X is S, SO, SO ２ The compound according to any one of claims 1 to 7, wherein the compound is selected from the group consisting of:

9. B1 is selected from the group consisting of halogen, CN, ethynyl, methyl optionally substituted with F, and C optionally substituted with OH. １－３ The compound according to any one of claims 1 to 8, wherein the heteroaryl is optionally substituted with a group selected from the group consisting of heterocycles optionally substituted with alkyl.

10. B1 is Cl, Br, CN, methyl, CF ３ , azetidinyl; CH ２ 10. The compound according to claim 9, selected from: azetidinyl substituted with OH; pyridinyl optionally substituted with a group selected from the group consisting of pyridinyl, pyrimidinyl, oxazolyl and thiazolyl.

11. B1 is a C group optionally substituted with halogen, CN, or F; １－３ Alkyl, and CONR ６ｂ R ７ｂ (R ６ｂ and R ７ｂ are independent and H, C １－３ selected from the group consisting of alkyl, cyclopropyl, and isopropyl; or R ６ｂ and R ７ｂ and, together with the nitrogen, may form a heterocycloalkyl.

12. R ５０ But, H, OH, OC １－６ Alkyl, C １－４ C substituted with at least one selected from the group consisting of alkyl, and phenyl, and phenyl substituted with one or more groups selected from the group consisting of OH and halogen. １－４ The compound according to any one of claims 1 to 11, wherein the compound is selected from the group consisting of alkyl.

13. 3-chlorophenyl 3-deoxy-3-[4-(3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,5-difluoro-4-methylphenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 2-(N-azetidinyl-carbonyl)-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-methylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-bromo-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 2-cyano-5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chloro-3-fluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(6-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(5-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(4-fluoropyridin-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1-methyl-1,2-pyrazol-3-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(1H-imidazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(oxazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(thiazol-2-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-[4-(4-chlorothiazol-2-yl)-1H-1,2-pyrazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-ethynylpyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,3-imidazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloro-[3,3-bis(hydroxymethyl)azetidin-1-yl]pyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 5-chloropyridin-3-yl 3-deoxy-3-[3-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-oxazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-thiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-deoxy-3-[5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-yl]-1-thio-α-D-galactopyranoside, 3,4-dichlorophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2-pyrazol-1-yl]-3-deoxy-2-O-methyl-1-thio-α-D-galactopyranoside, 5-chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside, and 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(2-hydroxythiazol-4-yl)-1H-1,2-pyrazol-1-yl]-2-O-methyl-1-thio-α-D-galactopyranoside; or a pharmaceutical salt or solvate thereof The compound according to any one of claims 1 to 12, selected from the group consisting of:

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

15. 15. The pharmaceutical composition of claim 14 for use in a method for treating a disorder associated with the binding of galectin-3 to a ligand in a mammal, including a human.

16. The disorders include inflammation; inflammation-induced thrombosis; atopic dermatitis; acute coronary syndromes; fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, ophthalmological fibrosis and dermal and cardiac fibrosis; focal fibrosis, Dupuytren's disease, Peyronie's disease; fibrotic complications of other treatments including coronary artery stents, biliary stents, cerebral artery stents, ureteral stents; scleroderma; scarring; keloid formation; COVID-19; acute lung injury; ARDS; viral pneumonitis. , abnormal scar formation; surgical adhesions; septic shock; cancer, colorectal cancer, other gastrointestinal cancer, pancreatic cancer, gastric cancer, biliary tract cancer, lung cancer, mesothelioma, breast cancer, ovarian cancer, uterine cancer, cervical cancer, fallopian tube cancer, brain cancer, medulloblastoma, glioma, meningioma, bone and muscle sarcoma and other sarcomas, leukemia and lymphoma, T-cell lymphoma; transplant rejection; metastatic cancer; aging; dementia; Alzheimer's disease; TGFβ-driven bone disease, osteogenesis imperfecta; pulmonary hypertension; autoimmune diseases, psoriasis, Rheumatoid arthritis, rheumatoid lung; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections, influenza virus, HIV, herpes virus, coronavirus, hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, ocular angiogenesis or diseases or conditions associated with ocular angiogenesis, angiogenesis associated with cancer; and eye diseases, age-related macular degeneration and corneal angiogenesis; atherosclerosis; metabolic diseases; diabetes; type I diabetes; type 2 diabetes; insulin resistance; obesity; Marfan syndrome; Loeys-Dietz syndrome; nephropathy; diastolic HF; fibrotic pulmonary complications of aPD1 and other CPI therapy; asthma and other interstitial lung diseases, Hermansky-Pudlak syndrome, liver disorders, non-alcoholic steatohepatitis or non-alcoholic fatty liver disease; and uterine diseases including uterine fibroids and uterine or cervical fibrosis.

16. The pharmaceutical composition for use according to claim 15, selected from the group consisting of:

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