Arabinose derivative compound, and composition comprising same for preventing or treating degenerative brain diseases

Abstract

The present invention relates to a compound represented by chemical formula I, or an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, the compound targeting the taste receptor GPCR T1R3 so as to have efficacy as a neuroregenerative and neuroprotective agent, and to the compound, a preparation method therefor, and a pharmaceutical composition comprising same.

Description

Arabinose derivative compound and composition containing the same for preventing or treating degenerative brain disease

[0001] The present invention relates to an arabinose derivative compound, and more particularly, to an arabinose derivative compound that targets the taste receptor GPCR T1R3 and has the effect of a brain nerve regeneration and protection agent, a method for producing the same, and a pharmaceutical composition comprising the same.

[0002] Dementia is a degenerative brain disease caused by Alzheimer's disease, vascular disease, and other causes. Among them, Alzheimer's disease is characterized by slow progression, starting with memory impairment in the early stages and gradually accompanied by impairments in other cognitive functions such as language and judgment, ultimately leading to the loss of all daily functions.

[0003] Approximately 60-70% of dementia patients are known to have Alzheimer's disease. Currently, commercially available medications include Aricept, Exelon, Razadine, and Namenda. However, these drugs only maintain cognitive function and temporarily alleviate symptoms, limiting their effectiveness. Meanwhile, no new Alzheimer's treatment has been approved since 2003.

[0004] Currently, most pathological studies on the cause of Alzheimer's disease have focused on β-Amyloid (Aβ) and Tau proteins. However, all of these have failed in clinical trials, necessitating the development of novel drugs based on novel targets. The present invention has developed a novel drug candidate for the treatment of dementia that can fundamentally treat the disease by targeting the T1R3 GPCR, a novel target that is differentiated from the most actively developed targets for inhibiting / removing the formation of β-amyloid plaques and Tau aggregates.

[0005] T1R3 (Taste receptor type 1 member 3) is a component protein of the taste receptors present on the tongue, the sweet taste receptors (T1R2 / T1R3) and the umami taste receptors (T1R1 / T1R3). It is a class C GPCR (G protein-coupled receptor). Recently, as it has been confirmed that T1R3 is expressed not only in the tongue but also in several major organs in the human body, research on the in vivo function of T1R3 is actively being conducted. T1R3 is particularly highly expressed in the hippocampus and cortex, which are closely related to AD dementia, and numerous studies are being conducted to prove the relationship between T1R3 and AD dementia.

[0006] Pharmacological proof of concepts of T1R3 as an AD target can be confirmed through the following four studies.

[0007] First, T1R3 KO mice, in which only the T1R3 gene is knocked out, have abnormally enlarged cell bodies in the hippocampal CA1 region of the brain, increasing neuritic density, and relatively reduced dendritic density, unlike normal mice. In addition, dendrite length is also increased compared to normal animals. Furthermore, when performing the novel object preference (NOP) and Morris water maze (MWM) tests, which are representative behavioral observation methods for evaluating cognitive function, learning, and memory, T1R3 mice show a clear difference in low interest in novel objects and learning and memory impairment, unlike normal mice. Furthermore, in various behavioral observations, including the open field test, T1R3 KO mice were confirmed to have low sociability, decreased exploratory behavior, and high anxiety response to novel spaces. These results are interpreted as suggesting that AD dementia and the function of T1R3 are very closely related.

[0008] Second, in signal transduction through T1R3 GPCR, T1R3 stimulates Gαs and Gαq, and 1) Gαs stimulation affects cAMP and calcium, and when PKA (protein kinase A) is activated by cAMP, CREB is phosphorylated to become pCREB, which binds to CRE (cAMP response element), a binding site on DNA, and is involved in the expression of BDNF, DCX, and MAP-2. In addition, 2) when Gαq is activated, PIP2 (phosphatidylinositol 4,5-bisphosphate) is converted into DAG (diacylglycerol) and IP3 (inositol triphosphate) by PLC (phospholipase C). When the generated IP3 binds to IP3R, an IP3 receptor in the ER (endoplasmic reticulum), calcium in the ER is released into the cell, binds to CaM (calmodulin), and activates CaN (calcineurin), a dephosphorylating enzyme. The activated CaN dephosphorylates and activates NFAT (nuclear factor of activated T-cells), a transcription factor that expresses genes related to axon growth and neurogenesis. NFAT binds to NFAT-RE, promoting transcription.

[0009] Third, the P / PS1 transgenic mouse is a representative AD model that increases the level of β-Amyloid (Aβ), the pathogenesis of AD dementia, and accumulates amyloid plaques in the brain. The hippocampus of the APP / PS1 transgenic mouse showed a decrease in DCX (Doublecortin), synaptophysin, and progranulin, which were confirmed to be significantly increased by T1R3 Agonist administration.

[0010] Lastly, it has been reported that when T1R3 expression is abnormal or reduced during the aging process, the perception of sweetness is reduced, and in particular, it is known that dementia patients, including AD, have a much reduced perception of sweetness and umami tastes compared to normal people.

[0011] Based on the above major literature review and experimental results, we confirmed that T1R3 in the hippocampus and cortex can be a good new target for AD dementia treatment. Compared to existing neurogenesis targets that are endogenous enzymes, the T1R3 target is a novel GPCR agonist, which has a significant difference.

[0012] Accordingly, the inventors of the present invention selected 12 extracts by searching through library data of about 4,500 kinds stored in the plant extract bank, selected one candidate extract through phenotype-based screening, and derived a pre-candidate substance as a single active ingredient confirmed to bind to GPCR T1R3 and be effective in AD dementia among various mixed components of the extract, developed a derivative compound showing a useful effect as an Alzheimer's treatment, and confirmed that it can be usefully used as a pharmaceutical composition for prevention or treatment, thereby completing the present invention.

[0013] [Prior Art Literature]

[0014] [Patent Document]

[0015] Republic of Korea Patent Publication No. 2010-0015967 (Published: February 12, 2010)

[0016] The basic object of the present invention is to provide a compound represented by the following chemical formula I, or an isomer, hydrate, solvate, prodrug or pharmaceutically acceptable salt thereof.

[0017] [Chemical Formula I]

[0018]

[0019] The specific form of the above chemical formula I is as described in this specification.

[0020] Another object of the present invention is to provide a composition containing the above-mentioned compound or an isomer, hydrate, solvate, prodrug or pharmaceutically acceptable salt thereof as an active ingredient.

[0021] Another object of the present invention is to provide a manufacturing method for manufacturing a compound of chemical formula 1.

[0022] To achieve the above purpose, one aspect of the present invention is a compound represented by the following chemical formula I, or an isomer, hydrate, solvate, prodrug or pharmaceutically acceptable salt thereof.

[0023] [Chemical Formula I]

[0024]

[0025] In the above chemical formula I,

[0026] R1, R2, and R3 are each hydrogen, hydroxy, methoxy, fluoro, azide, amine, 10-aminodecanoic, acetyl, or benzyl;

[0027] R4 is hydrogen or methyl;

[0028] X is oxygen, nitrogen, sulfur or -CH2-;

[0029] A is phenyl which is unsubstituted or substituted with Y;

[0030] Substituent Y is hydrogen, straight or branched chain C 1-3 At least one selected from the group consisting of alkyl, and halogen;

[0031] B is a direct bond, -[CH2] n -, -C(CH3)2-, -C(CF3)2-, -O-, -NH-, -SO2-, , n is an integer from 1 to 3;

[0032] Ring C is unsubstituted or substituted with Z. 5-7 Cycloalkyl, C5-7 heterocycloalkyl, phenyl, biphenyl, naphthyl, aryl or heteroaryl;

[0033] Substituent Z is a straight or branched chain C 1-6 At least one selected from the group consisting of alkyl, cycloalkyl, phenyl, heteroaryl, halogen, amine, cyano, nitro, alkoxy, and thiol.

[0034] The compound according to the present invention may be an arabinose derivative compound based on arabinose. As described above, the inventors of the present invention selected 12 extracts by searching through about 4,500 kinds of library data, and then selected one candidate extract through phenotype-based screening. Among the various mixed components of the selected extract, arabinose was derived as a pre-candidate substance that is a single active ingredient that has been confirmed to bind to GPCR T1R3 and to be effective in treating AD dementia, and then an arabinose derivative compound that shows useful effects as an Alzheimer's treatment was developed.

[0035] In the compound according to the present invention, R1, R2, and R3 of the above formula (I) are each hydrogen, hydroxy, methoxy, fluoro, azide, amine, 10-aminodecanoic, acetyl, or benzyl, and R4 is hydrogen or methyl. As an example of the present invention, it is possible that two or more of R1, R2, and R3 of the above formula (I) are hydroxy, and R4 is hydrogen. In addition, it is possible that R1, R2, and R3 of the above formula (I) are each hydroxy, and R4 is hydrogen.

[0036] In the compound according to the present invention, X in the chemical formula I is oxygen, nitrogen, sulfur or -CH2-. As an example of the present invention, it is possible that X in the chemical formula I is oxygen.

[0037] In the compound according to the present invention, A in the above formula I is unsubstituted phenyl or phenyl substituted with Y. As an example of the present invention, it is possible for A in the above formula I to be unsubstituted phenyl.

[0038] The compound according to the present invention is a compound in which the substituent Y of the above chemical formula I is hydrogen, straight chain or branched chain C 1-3 At least one selected from the group consisting of alkyl, and halogen. As an example of the present invention, A in the above chemical formula I is phenyl substituted with Y, and the substituent Y may be halogen.

[0039] As an example of the present invention, XA of the above chemical formula I is , and the substituent Y is a straight or branched chain C 1-3 It can be alkyl or halogen. In the present invention, B can be connected to the C2 to C6 positions of A, and B can be substituted at the C3 position, which is a meta position with respect to X in A (aryl group), or the C4 position, which is a para position.

[0040] The compound according to the present invention, wherein B in the above chemical formula I is a direct bond, -[CH2] n -, -C(CH3)2-, -C(CF3)2-, -O-, -NH-, -SO2-, As an example of the present invention, B of the above chemical formula I may be a direct bond. As an example of the present invention, B of the above chemical formula I may be -CH2-. As an example of the present invention, B of the above chemical formula I may be -O-.

[0041] The compound according to the present invention is wherein ring C of the chemical formula I is unsubstituted C 5-7 Cycloalkyl, C 5-7 Heterocycloalkyl, phenyl, biphenyl, naphthyl, aryl or heteroaryl; or ring C substituted with Z is unsubstituted or C substituted with Z 5-7 Cycloalkyl, C 5-7Heterocycloalkyl, phenyl, biphenyl, naphthyl, aryl or heteroaryl. The cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be a 1-membered, 2-membered or 3-membered ring compound, and may also be a 4-membered or more ring compound. As an example of the present invention, the ring C of the above formula I may be phenyl which is unsubstituted or substituted with Z. As an example of the present invention, the ring C of the above formula I may be naphthyl which is unsubstituted or substituted with Z, or heteroaryl.

[0042] As an example of the present invention, the B-ring C of the above chemical formula I is It is possible that the substituent Z in the present invention may be linked to or substituted at the ortho, meta, or para positions of ring C.

[0043] As an example of the present invention, the B-ring C of the above chemical formula I is It is possible.

[0044] The compound according to the present invention is a compound in which the substituent Z of the above chemical formula I is a straight or branched C 1-6 At least one selected from the group consisting of alkyl, cycloalkyl, phenyl, heteroaryl, halogen, amine, cyano, nitro, alkoxy, and thiol. As an example of the present invention, the substituent Z of the above chemical formula I is a straight or branched C 1-6 It can be alkyl, halogen, amine, or alkoxy.

[0045] A compound according to one embodiment of the present invention can be formed by including XA (with Y), B, and C (with Z) as moieties as shown in Table 1 below.

[0046]

[0047]

[0048]

[0049]

[0050]

[0051]

[0052]

[0053]

[0054]

[0055] (a) HRE assay: Confirmation of increased HRE expression by test substance compared to vehicle in HRE / Luc / HEK293 cells

[0056] * Less than 2x increase at 100uM,

[0057] ** More than doubled from 100uM,

[0058] *** More than doubled from 10uM

[0059] **** More than doubled from 1uM,

[0060] - Not implemented.

[0061] The compounds in Table 1 above can be represented in order by the compound names below.

[0062] <1> (2R,3R,4S,5S)-2-(4-benzylphenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0063] <2> (2R,3R,4S,5S)-2-(4-(4-methylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0064] <3> (2R,3R,4S,5S)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0065] <4> (2S,3R,4S,5S)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0066] <5> (3S,4S,5R,6R)-5-methoxy-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0067] <6> (2R,3S,4R,5S,6S)-2-(4-(4-methoxybenzyl)phenoxy)-6-methyltetrahydro-2H-pyran-3,4,5-triol,

[0068] <7> (2R,3R,4S,5S)-2-(4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0069] <8> (2R,3R,4S,5S)-2-(2-chloro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0070] <9> (2R,3R,4S,5S)-2-(4-(4-phenoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0071] <10> (2R,3R,4S,5S)-2-(4-(4-trifluoromethoxy)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0072] <11> (2R,3R,4S,5S)-2-(4-(4-(methylthio)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0073] <12> (2S,3R,4S,5S)-2-(4-(4-(dimethylamino)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0074] <13> (2R,3R,4S,5S)-2-(4-(4-fluorobenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0075] <14> (2R,3R,4S,5S)-2-(4-(4-chlorobenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0076] <15> (2R,3R,4S,5S)-2-(4-(3-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0077] <16> (2R,3R,4S,5S)-2-(4-(3,5-bis(trifluoromethyl)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0078] <17> (2R,3R,4S,5S)-2-(4-(3,4-dimethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-triol,

[0079] <18> (2R,3R,4S,5S)-2-(4-(3,4,5-trimethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0080] <19> (2R,3R,4S,5S)-2-(4-(naphthalen-2-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0081] <20> (2R,3R,4S,5S)-2-(4-(6-methoxynaphthalen-2-yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0082] <21> (2R,3R,4S,5S)-2-(4-(cyclopentylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0083] <22> (2R,3R,4S,5S)-2-(4-(cyclohexylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0084] <23> (2R,3R,4S,5S)-2-(4-(thiophen-3-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0085] <24> (2S,3R,4S,5S)-2-(4-(pyridin-3-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0086] <25> (2R,3R,4S,5S)-2-(3-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0087] <26> (2R,3R,4S,5S)-2-((4-benzylphenyl)thio)tetrahydro-2H-pyran-3,4,5-thiol,

[0088] <27> (2R,3R,4S,5S)-2-((4-(4-isopropylbenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triol,

[0089] <28> (2S,3R,4S,5S)-2-((4-(4-isopropylbenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triol,

[0090] <29> (2R,3R,4S,5S)-2-((4-(4-methoxybenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-thiol,

[0091] <30> (2R,3R,4S,5S)-2-(4-(2-(4-methoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0092] <31> (2R,3R,4S,5S)-2-(4-(2-(4-ethoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0093] <32> (2R,3R,4S,5S)-2-(4-(1,1,1,3,3,3-hexafluoro-2-(4-methoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0094] <33> (2R,3R,4S,5S)-2-(4-(para-tolyloxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0095] <34> (2R,3R,4S,5S)-2-(4-(3,5-dimethylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0096] <35> (2R,3R,4S,5S)-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0097] <36> (2R,3R,4S,5S)-2-(4-(4-(tert-butyl)phenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0098] <37> (2R,3R,4S,5S)-2-(4-(3-chloro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0099] <38> (2R,3R,4S,5S)-2-(3-chloro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0100] <39> (2R,3R,4S,5S)-2-(4-(4-ethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0101] <40> (2R,3R,4S,5S)-2-(3-chloro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0102] <41> (2R,3R,4S,5S)-2-(2-fluoro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0103] <42> (2R,3R,4S,5R)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0104] <43> (2R,3R,4S,5R)-2-(4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0105] <44> (2R,3R,4S,5S)-2-(4-(4-isoproxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0106] <45> (2R,3R,4S,5S)-2-(4-(4-(cyclopentyloxy)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0107] <46> (2R,3R,4S,5S)-2-(2-fluoro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0108] <47> (2R,3R,4S,5S)-2-(3-fluoro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0109] <48> (2R,3R,4S,5S)-2-(3-fluoro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0110] <49> (2R,3R,4S,5S)-2-(4-(2-chloro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0111] <50> (2R,3R,4S,5S)-2-(4-(2-fluoro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0112] <51> (2R,3R,4S,5S)-2-(2-chloro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0113] <52> (2R,3R,4S,5S)-2-(4-((4'-isopropyl-[1,1'-biphenyl]-4-yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0114] <53> (2R,3R,4S,5S)-2-(4-((5-methoxybenzo[d]oxazol-2-yl)methol)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0115] <54> (2R,3R,4S,5S)-2-(3-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0116] <55> (2R,3R,4S,5S)-2-(4-(4-methoxyphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0117] <56> (2R,3R,4S,5R)-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0118] <57> (2R,3R,4S,5S)-2-(2-chloro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0119] <58> (2R,3R,4R,5S)-5-fluoro-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0120] <59> (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0121] <60> (2R,3R,4S,5S)-2-(4-(4-isopropylphenoxy)phenoxy)-4-methoxytetrahydro-2H-pyran-3,5-diol

[0122] <61> (2R,3R,4R,5S)-2-(4-(4-isopropylphenoxy)phenoxy)-5-methoxytetrahydro-2H-pyran-3,4-diol,

[0123] <62> (3S,4S,5R,6R)-6-(4-(4-isopropylphenoxy)phenoxy)-5-methoxytetrahydro-2H-pyran-3,4-diol,

[0124] <63> (3S,4S,5R,6R)-5-fluoro-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0125] <64> (2R,3R,4R,5R)-5-fluoro-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0126] <65> (3S,4S,5S,6R)-5-fluoro-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0127] <66> (3S,4R,6R)-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0128] <67> (2R,3R,4S,5R)-2-(2-chloro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0129] <68> (2R,3R,4S,5S)-2-(2-fluoro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0130] <69> (3S,4R,5R,6R)-5-azido-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0131] <70> (3S,4R,5R,6R)-5-amino-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol,

[0132] <71> (4-methoxyphenyl)(4-(((2R,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone,

[0133] <72> 4-(4-(((2S,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)benzoyl)benzonitrile,

[0134] <73> (2R,3R,4S,5S)-2-(4-(((1r,4R)-4-ethylcyclohexyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0135] <74> (2R,3R,4S,5S)-2-(4-(((1r,4R)-4-isopropylcyclohexyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0136] <75> (2S,3R,4S,5S)-2-(4-(pyrrolidin-1-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0137] <76> (2S,3R,4S,5S)-2-(4-(morpholinomethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0138] <77> (3S,4R,5R,6R)-5-azido-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran)-3,4-diol,

[0139] <78> (3S,4R,5R,6R)-5-azido-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran)-3,4-diol,

[0140] <79> (2R,3R,4S,5S)-4,5-dihydroxy-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3-yl 10-aminodecanoate,

[0141] <80> (2R,3R,4S,5S)-2-((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol,

[0142] <81> (2R,3R,4S,5S)-2-(4-(6-methoxybenzofuran-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0143] <82> (2R,3R,4S,5S)-2-(4-(5-methoxy-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0144] <83> (2S,3R,4S,5S)-2-(4-(5-methoxy-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0145] <84> (2R,3R,4S,5S)-2-((4'-methoxy-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol,

[0146] <85> (2R,3R,4S,5S)-2-(4-(6-methoxypyridin-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0147] <86> (2R,3R,4S,5S)-2-((4'-isopropyl-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol,

[0148] <87> (2S,3R,4S,5S)-2-((4'-isopropyl-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol,

[0149] <88> (2R,3R,4S,5S)-2-(4-(6-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0150] <89> (2S,3R,4S,5S)-2-(4-(6-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0151] <90> (2R,3R,4S,5S)-2-(4-(5-methyl-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0152] <91> (2R,3R,4S,5S)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0153] <92> (2S,3R,4S,5S)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0154] <93> (2R,3R,4S,5R)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0155] <94> (2S,3R,4S,5R)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0156] <95> (2R,3R,4S,5S)-2-(4-(6-ethylbenzofuran-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0157] <96> (2S,3R,4S,5S)-2-(4-(6-ethylbenzofuran-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0158] <97> (2R,3R,4S,5S)-2-(3-(7-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0159] <98> (2S,3R,4S,5S)-2-(3-(7-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0160] <99> (2R,3R,4S,5S)-2-(2-chloro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0161] <100> (2S,3R,4S,5S)-2-(2-chloro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0162] <101> (2R,3R,4S,5R)-2-(2-fluoro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0163] <102> (2S,3R,4S,5S)-2-(2-chloro-4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0164] <103> (2R,3R,4S,5S)-2-(2-chloro-4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0165] <104> (2S,3R,4S,5S)-2-(2-fluoro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0166] <105> (2R,3R,4S,5S)-2-(2-fluoro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0167] <106> (2S,3R,4S,5S)-2-(3-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0168] <107> (2R,3R,4S,5S)-2-(3-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0169] <108> (2S,3R,4S,5S)-2-(4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0170] <109> (2R,3R,4S,5S)-2-(4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0171] <110> (2R,3R,4S,5S)-2-(4-phenethylphenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0172] <111> (2R,3R,4S,5S)-2-(4-((E)-styryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0173] <112> (2R,3R,4S,5S)-2-(4-(bis(4-methoxyphenyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0174] <113> (2R,3R,4S,5S)-2-((4'-(4-isopropylbenzyl)-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol,

[0175] <114> Furan-2-yl(4-(((2S,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone,

[0176] <115> Furan-2-yl(4-(((2R,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone,

[0177] <116> (2R,3R,4S,5S)-2-(4-(4-methoxyphenethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0178] <117> (2R,3R,4S,5S)-2-(4-(4-isopropylphenethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0179] <118> (2R,3R,4S,5S)-2-(4-((E)-4-methoxystyryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0180] <119> (2R,3R,4S,5S)-2-(4-((E)-4-isopropylstyryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0181] <120> (2R,3R,4S,5S)-2-(4-(benzo[d][1,3]dioxol-5-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0182] <121> (2R,3R,4S,5S)-2-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,

[0183] <122> (2R,3R,4S,5S)-2-((4'-chloro-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol,

[0184] <123> (2R,3R,4S,5S)-2-((4''-isopropyl-[1,1':4',1''-terphenyl-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol,

[0185] <124> (2R,3R,4S,5S)-2-(3-(phenylethynyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol.

[0186] The compound according to the present invention is <1> Inland <124> It may be one selected from the group consisting of. Such a compound may be an arabinose derivative compound based on arabinose. Among them, the compound of formula I according to the present invention is <1> Inland <57> , <60> Inland <62> , <67> Inland <68> , <71> Inland <76> , and <80> Inland <124> It is possible that any one of the groups consisting of

[0187] As an example of the present invention, the above-described compound may have brain nerve regeneration and protection functions by targeting GPCR T1R3. As described above, the inventors of the present invention identified arabinose as a pre-candidate, a single active ingredient confirmed to bind to GPCR T1R3 and be effective in treating AD dementia, among various mixed components of a number of extracts, and then developed an arabinose derivative compound that exhibits useful effects as an Alzheimer's treatment. In addition, as can be confirmed in the experimental examples described below, the developed compound was confirmed to induce increased activity of the hypoxia response element (HRE).

[0188] As an example of the present invention, the above-described compound can be used for the prevention or treatment of degenerative brain diseases. As can be confirmed in the experimental examples described below, the compound according to the present invention exhibited excellent effects in a scopolamine-induced cognitive impairment model experiment and a long-term memory enhancement (LTP) experiment.

[0189] Another embodiment of the present invention is a pharmaceutical composition for preventing or treating degenerative brain diseases, comprising the compound described above, an isomer, hydrate, solvate, prodrug, or pharmaceutically acceptable salt thereof. Since the compound has cognitive impairment-improving and long-term memory-enhancing effects, it is possible to prevent or treat degenerative brain diseases.

[0190] In the present specification, the degenerative brain disease is not particularly limited and may include various diseases known in the art. For example, the degenerative brain disease may be at least one selected from the group consisting of stroke, dementia, Parkinson's disease, dizziness, epilepsy, peripheral neuromuscular disease, brain tumor, brain lesion disorder, brain edema, paraplegia, meningitis, encephalitis, concussion, pituitary tumor, Huntington's disease, tuberculous meningitis, ataxia, mad cow disease, glioblastosis, agoraphobia, cluster headache syndrome, amnesia, Dandy-Walker syndrome, Tourette syndrome, Wernicke-Koskoff syndrome, meningioma, and Gerstmann syndrome. In addition, the degenerative brain disease may be at least one selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, tauopathy, vascular dementia, acute stroke, trauma, cerebrovascular disease, brain cord trauma, spinal cord trauma, peripheral neuropathy, retinopathy, and glaucoma.

[0191] As an example of the present invention, the above composition may have a brain nerve regeneration and protection function by targeting GPCR T1R3.

[0192] A pharmaceutically acceptable salt of the compound of formula I of the present invention may be a hydrochloride, sulfate, acetate, formate, succinate, malate, fumarate, toluenesulfonate or methanesulfonate of the compound of formula I.

[0193] A pharmaceutical composition for preventing or treating a degenerative brain disease can be provided, comprising a compound of chemical formula I of the present invention and a pharmaceutically acceptable excipient or carrier.

[0194] The above pharmaceutical composition can be prepared according to conventional methods using one or more pharmaceutically acceptable adjuvants or excipients. The adjuvants include, in particular, diluents, sterile aqueous media, and various non-toxic organic solvents.

[0195] The pharmaceutical composition may be provided in the form of tablets, pills, granules, powders, aqueous solutions or suspensions, injectable solutions, elixirs or syrups, and may further contain sweeteners, flavoring agents, coloring agents or stabilizers to obtain pharmaceutically acceptable preparations.

[0196] The choice of vehicle and the amount of active ingredient within the vehicle are generally determined by the solubility and chemical properties of the active compound, the particular mode of administration, and the conditions to be observed in pharmaceutical practice. For example, excipients such as lactose, sodium citrate, calcium carbonate, and dicalcium phosphate, combined with lubricants such as magnesium stearate, sodium lauryl sulfate, and talc, and disintegrants such as starch, alginic acid, and certain complex silicates can be used for the manufacture of tablets.

[0197] For the manufacture of capsules, lactose and high molecular weight polyethylene glycol are advantageously used. When aqueous suspensions are used, they may contain emulsifiers or agents that facilitate suspension, and diluents such as sucrose, ethanol, polyethylene glycol, propylene glycol, glycerol, or chloroform, or mixtures thereof, may also be used.

[0198] Another embodiment of the present invention is a food composition for preventing degenerative brain diseases, comprising the compound described above, an isomer, hydrate, solvate, prodrug, or pharmaceutically acceptable salt thereof. The food composition of the present invention can take various forms, such as a health functional food, a health food, or a general food.

[0199] According to another aspect of the present invention, a method for preparing a compound of formula I is provided, comprising the steps of: (i) reacting an arabinose derivative compound represented by formula a or a' with a compound represented by formula b to obtain a compound represented by formula c in the form of a mixture of α and β forms or c' in the form of α-form; and (ii) hydrolyzing the compound c or c' using sodium methoxide to obtain a target compound, formula 1.

[0200] <Reaction Formula 1>

[0201]

[0202] The present invention can provide a compound represented by the above chemical formula I, or an isomer, hydrate, solvate, prodrug or pharmaceutically acceptable salt thereof.

[0203] The present invention can provide a composition containing the above-mentioned compound or an isomer, hydrate, solvate, prodrug or pharmaceutically acceptable salt thereof as an active ingredient.

[0204] The present invention can provide a manufacturing method for manufacturing a compound of the above chemical formula 1.

[0205] Hereinafter, the present invention will be described in more detail with reference to the following examples and drawings. However, the description of the following examples and drawings is intended only to specifically illustrate specific embodiments of the present invention, and is not intended to limit or restrict the scope of the present invention to the contents described therein.

[0206] In the manufacturing examples and examples of the present invention, the compounds were purified by the following method and their structures were analyzed.

[0207] 1. HPLC analysis conditions

[0208] - Device name: Waters Arc HPLC Core

[0209] - Column: XBridge C18 5μm 4.6x250mm, 40℃

[0210] - Mobile phase: 20% → 95% acetonitrile / H2O + 0.1% formic acid

[0211] - Analysis time: 20 minutes, flow rate: 1 mL / min

[0212] - UV detector: 254 nm

[0213] 2. LC-MS analysis conditions

[0214] -Device name: Agilent 1260

[0215] - Column: Agilent ZORBAX SB-C18 1.8um, 50 x 2.1 mm, 45℃

[0216] - Mobile phase: Acetonitrile / H2O + 0.1% Formic acid

[0217] - Flow rate: 0.4 mL / min

[0218] - UV detector: 254 and 300 nm

[0219] 3. NMR

[0220] - Device name: Agilent technologies 400-MR (400 MHz)

[0221] Commercially available reagents were used without further purification. In the present invention, room temperature (rt) or ambient temperature refers to a temperature of 5 to 40°C, for example, 10 to 30°C or 15 to 27°C, and is not strictly limited to the above range. Concentration under reduced pressure or solvent distillation was performed using a rotary evaporator.

[0222] Manufacturing Example 1. Synthesis of benzyl phenol derivatives

[0223] Step 1-1. Grignard reaction

[0224]

[0225] Compound 1 (30 mmol) was added to anhydrous THF (150 mL) at 0 °C under the presence of argon, followed by dropwise addition of compound 2 (75 mmol, 2.5 equivalents) and stirring at room temperature overnight. Aqueous ammonium chloride solution was added to the residue, and extraction was performed with ethyl acetate. The combined organic layers were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20% EtOAc in hexane) to obtain compound 3.

[0226] Step 1-2. Reduction reaction of benzyl alcohol

[0227]

[0228] Compound 3 (4.0 mmol) was suspended in anhydrous DCM (12.0 mL) under the presence of argon, then triethylsilane (8 mmol, 2.0 equiv) and BF 3· Et2 (6 mmol, 1.5 equiv) was added, and the mixture was stirred at 0 °C for 45 min. After stirring at room temperature for another 30 min, aqueous sodium bicarbonate solution was added to the mixture, and extraction was performed with DCM. The combined organic layers were washed with a saturated brine solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified with (100-200 silica gel, 100 g, 20-33% EtOAc in hexane) to give compound 4.

[0229] Step 2-1. Synthesis of 4-((4-(dimethylamino)phenyl)(hydroxy)methyl)phenol

[0230]

[0231] Under an argon atmosphere, 9.6 mL of 2.5 M n-BuLi was added dropwise to a stirred solution of compound 6 (24 mmol, 2.4 equiv) in 80 mL of anhydrous THF at -78 °C and stirred for 30 min. A solution of compound 5 (10 mmol) in 20 mL of anhydrous THF was added dropwise and stirred at room temperature for 2 h. When the reaction was confirmed to be complete, extraction was performed with 200 mL of a saturated aqueous solution of NaHCO3. The mixture was dried over Na2SO4, filtered, and concentrated under reduced pressure. The reaction mixture was filtered with a 9% EtOAc solution in hexane to obtain compound 7 (1.87 g, 77%) as a white solid.

[0232] Step 2-2. Synthesis of 4-(4-(dimethylamino)benzyl)phenol

[0233]

[0234] Under an argon atmosphere, TMSCl (39.53 mmol, 7 equiv) was added dropwise to a stirred solution of compound 7 (5.65 mmol) and sodium iodide (39.53 mmol, 7 equiv) in 56 mL of anhydrous acetonitrile, and the mixture was stirred at room temperature. Once the reaction was confirmed to be complete, the mixture was diluted with DCM and washed with 100 mL of a saturated aqueous solution of Na2S2O3. The mixture was extracted with 100 mL of EtOAc, dried over Na2SO4, and filtered. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (100-200 silica gel, 100 g, 33% EtOAc in Hexane) to give compound 8 (768 mg, 60%) as a white solid.

[0235] Step 3-1. Synthesis of (4-methoxyphenyl)(pyridin-3-yl)methanol

[0236]

[0237] To a stirred solution of compound 10 (12 mmol, 2.4 equiv) in 50 mL of anhydrous THF under the presence of argon, 4.8 mL of 2.5 M n-BuLi was added dropwise at -78 °C and stirred for 30 min. Compound 9 (5 mmol) was added dropwise and stirred at room temperature for 4 h. When the reaction was confirmed to be complete, 50 mL of saturated aqueous NaHCO3 solution was added and extracted with 100 mL of EtOAc. The residue was dried over Na2SO4, filtered, and concentrated under reduced pressure. The reaction mixture was purified by column chromatography (100-200 silica gel, 100 g, using a 50% EtOAc solution in hexane) to give compound 11 (689 mg, 64%) as a white solid.

[0238] Step 3-2.3 Synthesis of (4-methoxybenzyl)pyridine

[0239]

[0240] To a stirred solution of compound 11 (3.2 mmol) and sodium iodide (22.1 mmol, 7 equiv) in 32 mL of anhydrous acetonitrile under the presence of argon, TMSCl (22.1 mmol, 7 equiv) was added dropwise, and the mixture was stirred at room temperature. Once the reaction was complete, the mixture was diluted with DCM and washed with 100 mL of a saturated aqueous solution of Na2S2O3. The mixture was extracted with 100 mL of EtOAc, dried over Na2SO4, and filtered. Compound 12 (383 mg, 61%) was purified by column chromatography (100-200 silica gel, 100 g, 50% EtOAc in Hexane) as a white solid.

[0241] Step 3-3.4-Synthesis of (pyridin-3-ylmethyl)phenol

[0242]

[0243] To a stirred solution of compound 12 (1.857 mmol) in anhydrous DCM under an argon atmosphere, 1 M BBr3 (2.043 mmol, 1.1 equiv) was added dropwise at -78 °C and stirred at room temperature for 7 h. When the reaction was confirmed to be complete, 3.7 mL of saturated aqueous NaHCO3 solution was added and extracted with DCM (7.4 mL × 2). The mixture was dried over Na2SO4, filtered, and concentrated under reduced pressure. The reaction mixture was purified by column chromatography (100-200 silica gel, 100 g, 33% EtOAc in Hexane) to give compound 13 (250 mg, 73%) as a white solid.

[0244] Step 4-1.3-Chloro-4-methoxybenzaldehyde synthesis

[0245]

[0246] Under an argon atmosphere, sulfuryl chloride (17.6 mmol, 1.2 equivalents) was added dropwise to a mixture of 4-methoxy-benzaldehyde 14 (14.7 mmol) and pyridine (30 μL, catalytic) over 30 minutes, maintaining the internal reaction temperature between 25 and 30 °C. During this time, gas was evolved vigorously. The reaction mixture was stirred at room temperature for 30 minutes, then heated to 70 °C and stirred for 4 hours. The reaction mixture was concentrated under reduced pressure to remove excess reactants, diluted with 50 ml of isopropyl ether, and 500 ml of hexane was added with vigorous stirring, from which a precipitate was formed. The solid was washed with hexane, filtered, and dried in vacuo to obtain compound 15 (2.1 g, 83%).

[0247] Step 4-2. Synthesis of (3-chloro-4-methoxyphenyl)(4-isopropylphenyl)methanol

[0248]

[0249] Compound 15 (10 mmol) was added to anhydrous THF (50 mL) at 0 °C under the presence of argon, followed by dropwise addition of compound 16 (25 mmol, 2.5 equiv) and stirring at room temperature overnight. Aqueous ammonium chloride solution was added to the residue, and extraction was performed with ethyl acetate. The combined organic layers were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20% EtOAc in Hexane) to give compound 17 (2.3 g, 79%).

[0250] Step 4-3. Synthesis of 4-(4-(dimethylamino)benzyl)phenol

[0251]

[0252] In the presence of argon, compound 3 (4.0 mmol) was added to a stirred solution of anhydrous DCM (12.0 mL) and triethylsilane (8 mmol, 2.0 eq) and BF 3· Et2 (6 mmol, 1.5 equiv) was added, and the mixture was stirred at 0°C for 45 min. After stirring at room temperature for another 30 min, aqueous sodium bicarbonate solution was added to the mixture, and extraction was performed with DCM. The combined organic layers were washed with a saturated brine solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by (100-200 silica gel, 100 g, 20-33% EtOAc in hexane) to give compound 18 (790 mg, 72%).

[0253] Step 4-4.2 Synthesis of chloro-4-(4-isopropylbenzyl)phenol

[0254]

[0255] To a stirred solution of compound 18 (2.88 mmol) in anhydrous DCM under an argon atmosphere, 1 M BBr3 (3.17 mmol, 1.1 equiv) was added dropwise at -78 °C and stirred at room temperature for 7 h. When the reaction was confirmed to be complete, 3.7 mL of saturated aqueous NaHCO3 solution was added and extracted with DCM (15 mL × 2). The mixture was dried over Na2SO4, filtered, and concentrated under reduced pressure. The reaction mixture was purified by column chromatography (100-200 silica gel, 100 g, 33% EtOAc in Hexane) to give compound 19 (571 mg, 76%) as a white solid.

[0256] Step 5 Asymmetric alkylation of bisphenol compounds having substituents

[0257]

[0258] Bisphenol compound 20 (43 mmol) and potassium carbonate (65 mmol, 1.5 equivalents) were mixed in DMF (20 ml), and then iodoalkyl (39 mmol, 0.9 equivalents) was added to 25 o The reaction was carried out at C for 12 hours. After completion of the reaction, potassium carbonate was filtered off, the filtrate was extracted with EtOAc, and then the moisture was removed with anhydrous magnesium sulfate and filtered. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (100-200 silica gel, 100 g, 20% EtOAc in hexane) to produce compound 21.

[0259] Step 6-1 Synthesis of iodobenzyl alcohol derivatives

[0260]

[0261] Compound 22 (30 mmol) was added to anhydrous THF (80 mL) at -40 °C under the presence of argon, followed by dropwise addition of compound isopropylmagnesium chloride (33 mmol, 1.1 equivalents). After 30 minutes, 23 (33 mmol, 1.1 equivalents) was added dropwise. Aqueous ammonium chloride solution was added to the residue, and extraction was performed with ethyl acetate. The combined organic layers were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 10% EtOAc in hexane) to obtain compound 24.

[0262] Step 6-2 Iodobenzyl alcohol reduction reaction

[0263]

[0264] Compound 24 (10.0 mmol) was suspended in anhydrous DCM (100.0 mL), and triethylsilane (15 mmol, 1.5 equiv) and BF3·Et2 (20 mmol, 2.0 equiv) were successively added dropwise at 0°C, and the mixture was stirred for 2 h. After completion of the reaction, aqueous sodium bicarbonate solution was added to the mixture, and the mixture was extracted with DCM. The combined organic layers were washed with a saturated brine solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified with (100-200 silica gel, 100 g, 10% EtOAc in hexane) to obtain compound 25.

[0265] Step 6-3 Synthesis of benzylbenzenethiol

[0266]

[0267] Compound 25 (9.4 mmol) was suspended in anhydrous DMSO (19 mL) under argon, and CuSO4 (0.47 mmol, 5 mol%) and KOH (47 mmol, 5.0 equivalents) were added sequentially. 26 was slowly added dropwise to the mixture and stirred for 20 hours. After confirming the completion of the reaction, the mixture was cooled to room temperature, neutralized with 5% aqueous HCl solution, and then aqueous sodium bicarbonate solution was added, followed by extraction with EtOAc. The combined organic layers were washed with a saturated brine solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by (100-200 silica gel, 100 g, Hexane) to obtain compound 27.

[0268] Step 7-1 Synthesis of benzyl derivatives

[0269]

[0270] Compound 28 (0.715 mmol) and celite (71.5 g) were suspended in anhydrous DCM under argon, PCC (2 equivalents) was added, and the mixture was stirred at room temperature for 3 hours. The mixture was filtered through celite, and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20% EtOAc in hexane) to give compound 29.

[0271] Step 7-24-(4-hydroxybenzoyl)benzonitrile synthesis

[0272]

[0273] Compound 30 (0.611 mmol) and Pyridine . A mixture of HCl (10 equivalents) at 210 oThe mixture was stirred at C for 4 hours. Water was added to the mixture, and extraction was performed with ethyl acetate. The combined organic layers were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20-33% EtOAc in hexane) to obtain compound 31.

[0274] Step 8-1 Amide reaction

[0275]

[0276] Compound 32 (8.76 mmol), DMAP (2.19 mmol, 0.2 equiv), and TEA (32.86 mmol, 3 equiv) were added to THF (50 mL) and filled with argon gas. After cooling to 0°C, compound 33 (8.76 mmol, 1 equiv) was added dropwise and stirred at room temperature overnight. A saturated solution of NaHCO3 was added to the mixture and extracted with DCM. The organic layer was washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (EA:DCM:Hexane=1:6:12) to obtain compound 34.

[0277] Step 8-2 Cyclization reaction

[0278]

[0279] Compound 35 (4.1 mmol), CuI (1.0 mmol, 0.25 equiv), 1,10-Phen (3.08 mmol, 1.1 equiv), and Cs2CO3 (12.3 mmol, 3 equiv) were sequentially added to 1,4-dioxne (45 mL) and the mixture was filled with argon gas. The mixture was refluxed at 105 °C and stirred overnight. After removing diode by concentration under reduced pressure, the mixture was diluted with EA, filtered through Celite, and concentrated. The mixture was purified by column chromatography (100-200 silica gel, 5 g, EA:DCM=1:1) to obtain compound 36.

[0280] Step 8-3 Debenzylation reaction

[0281]

[0282] Compound 37 (3.95 mmol) was dissolved in EtOH:THF = 1:2 (80 mL), and 10% Pd / C (wt 55%, 250 mg) was added. The mixture was replaced with hydrogen gas using a hydrogen balloon. After stirring overnight at room temperature, the mixture was filtered through Celite and concentrated under reduced pressure to obtain compound 38.

[0283] Step 93 Synthesis of (7-isopropylbenzo[d]oxazol-2-yl)phenol.

[0284]

[0285] Compounds 39 (5.29 mmol) and 40 (5.29 mmol, 1 equivalent) were added to ODCB (1,2-Dichlorobenzene) (50 mL), and PTSA-H2O (15.87 mmol, 3 equivalents) was added while stirring at room temperature. The mixture was refluxed at 172 °C for 5 hours and then slowly cooled to 0 °C. A saturated solution of NaHCO3 was added to the mixture and stirred vigorously for 10 minutes. A small amount of hexane was added and then filtered. The solid was washed with a large amount of water and hexane and dried to obtain compound 41.

[0286] Step 10-1 Halogen substitution reaction

[0287]

[0288] Compound 42 (8.73 mmol), compound 43 (10.48 mmol, 1.2 equivalents), and K2CO3 (17.46 mmol, 2 equivalents) were added to acetone (30 mL), and reflux stirring was continued overnight. The mixture was filtered to remove the solid, concentrated under reduced pressure, and purified by column chromatography (Haxane:DCM=3:2) to obtain compound 44.

[0289] Step 10-2 Cyclization reaction.

[0290]

[0291] Compound 45 (4.44 mmol) and Amberlyst 15 (200 mg) were added to toluene (20 mL), and reflux stirring was continued for 4 hours. After cooling the mixture, it was filtered to remove the solid, concentrated under reduced pressure, and purified by column chromatography (Haxane:DCM=9:1) to obtain compound 46.

[0292] Step 10-3 Synthesis of 3-(7-isopropylbenzo[d]oxazol-2-yl)phenol

[0293]

[0294] Compound 47 (2.5 mmol) was dissolved in DCM (15 mL) and replaced with argon gas. 1 M BBr3 (6.2 mmol, 1.5 equiv) was added dropwise at 0°C and stirred at room temperature for 1 h. After cooling to 0°C, 3 mL of MeOH was added and stirred for 10 min. The mixture was concentrated under reduced pressure to remove the solvent and diluted with EA. Saturated aqueous NaHCO3 solution was added and extracted with EA. The mixture was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The mixture was purified by column chromatography (EA:DCM=15–25%) to obtain compound 48.

[0295] Step 11-14 Synthesis of (hydroxybis(4-methoxyphenyl)methyl)phenol

[0296]

[0297] Under argon, a mixed solution of anhydrous THF (50 ml) and compound 49 (30.0 mmol) was stirred at -78 °C, and 2.5 M n-BuLi (30.0 mmol) was slowly added dropwise, and the mixture was stirred for 30 minutes. After compound 50 (10.0 mmol) was added dropwise, the temperature was gradually increased, and the mixture was stirred at room temperature for 6 hours. When the reaction was confirmed to be complete, 50 ml of saturated aqueous NaHCO3 solution was added, and extraction was performed with EtOAc. After drying over anhydrous magnesium sulfate, the mixture was filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 40% EtOAc in hexane) to obtain compound 51.

[0298] Step 11-24 Synthesis of ((4-methoxycyclohexa-2,4-dien-1-yl)(4-methoxyphenyl)methyl)phenol

[0299]

[0300] Under argon, a mixed solution of anhydrous MeCN (45 ml) and compound 52 (4.5 mmol) was stirred at 0 °C, and sodium borohydride (4.5 mmol) was slowly added dropwise. The mixture was stirred for 30 minutes. Then, trimethylsilyl chloride (9.0 mmol) and potassium iodide (4.5 mmol) were sequentially added dropwise at 0 °C, and the temperature was gradually increased, and the mixture was stirred at room temperature for 3 hours. When the reaction was confirmed to be complete, 50 ml of a saturated aqueous solution of NaHCO3 and 50 ml of a saturated aqueous solution of Na2S2O3 were added, and the mixture was extracted with EtOAc. The mixture was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 25% EtOAc in hexane) to obtain compound 53.

[0301] Step 12-1 Synthesis of 2-furoyl chloride

[0302]

[0303] Compound 54 (40 mmol) and DMF (0.01 equiv) were added to anhydrous DCM (120 mL) in the presence of argon, and (COCl)2 (1.2 equiv) was added dropwise at 0°C, followed by stirring at room temperature overnight. The residue was concentrated in vacuo to obtain compound 55.

[0304] Step 12-2 Synthesis of furan-2-yl(4-hydroxyphenyl)methanone

[0305]

[0306] Compound 56 (3.83 mmol) and phenol (1.05 equiv) were added to anhydrous DCM (4.3 mL) under argon, followed by dropwise addition of AlCl3 (1.4 equiv) at 0°C, and the mixture was stirred at room temperature overnight. Ice water was added to the mixture, and the organic layer was washed with 1 N HCl and water. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 10% EtOAc in hexane) to give compound 57.

[0307] Step 13 Synthesis of phenoxyphenol derivatives

[0308]

[0309] Compounds 58 (1.0 mmol), 59 (1.2 mmol, 1.2 equiv) and CuFe2O4 (0.05 mmol) were suspended in methanol (2 ml) and stirred for 24 h. The reaction mixture was concentrated in vacuo, and water was added to the residue, which was then extracted with DCM. The combined organic layers were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 25% EtOAc in Hexane) to give compound 60.

[0310] Step 14-1 Sonogashira reaction

[0311]

[0312] 61 (2 mmol) and 62 (1.5 mmol) were added to anhydrous THF (80 mL) together with PPh3 (0.02 equiv.), CuI (0.01 equiv.), and PdCl2(PPh3)2 (0.02 equiv.) at room temperature, followed by the addition of TEA (80 mL). The mixture was stirred at 80 °C for 8 h. After the reaction was completed, the mixture was cooled to room temperature, distilled water was added, and the mixture was extracted with EA. The organic layer was washed with a saturated brine solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 50% EtOAc in Hexane) to give compound 63.

[0313] Step 14-2 Demethylation reaction

[0314]

[0315] Compound 64 (0.6 mmol) was dissolved in anhydrous DCM (10 mL) under the presence of argon, and BBr3 (1.2 equivalents) was slowly added dropwise at -20 °C and stirred for 1 hour. After stirring for an additional 12 hours at room temperature, if no reaction occurred, the mixture was adjusted to pH 7 by adding aqueous sodium bicarbonate solution and extracted with EA. The organic layer was combined, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20% EtOAc in hexane) to obtain compound 65.

[0316] Step 15-1 Wittig reaction

[0317]

[0318] To compound 66 (1 mmol) was dissolved in anhydrous THF (2 mL) under the presence of argon. n-BuLi (2.5 M in Hexane, 0.5 equiv) was slowly added dropwise at -10 °C and stirred for 1 hour. 67 (0.5 equiv) was dissolved in anhydrous THF (1 mL), slowly added dropwise, and stirred for 1 hour. After stirring at room temperature for 12 hours, the mixture was extracted with DCM. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20% EtOAc in Hexane). The obtained compound was dissolved in Hexane (10 mL) and stirred at 70 °C for 1 hour. The organic layer was extracted with DCM and Na2S2O3(aq), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to obtain compound 68.

[0319] Step 15-2 Reduction reaction

[0320]

[0321] Compound 68 (1 mmol) was dissolved in anhydrous methanol (5 mL) in the presence of hydrogen, 10% Pd / C (5 mg) was added, and the mixture was stirred. After filtering through Celite, the filtrate was concentrated under vacuum. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20% EtOAc in hexane) to obtain compound 69.

[0322] Manufacturing Example 2. Introduction of a substituent in the α / β form to an arabinose derivative having a protecting group.

[0323]

[0324] In the presence of argon, compound b (2.4 mmol, 1.5 equivalents) to be reacted with compound 70 (1.6 mmol) was added to 16 ml of anhydrous DCM and mixed, then 0 oWhile stirring at C, boron trifluoride diethyl etherate (6.4 mmol, 4 equivalents) was slowly added and reacted at room temperature for 4 to 12 hours. After completion of the reaction, 100 ml of saturated potassium carbonate aqueous solution was added, the organic layer was separated, washed with water, concentrated under reduced pressure, and purified by column chromatography (100-200 silica gel, 100 g, 10-33% EtOAc in Hexane) to obtain compounds 71 ​​and 72 in the α / β form (10:1 to 1:1 ratio).

[0325] *b was synthesized using the method from step 1-1 to step 15-2 of Manufacturing Example 1.

[0326] Manufacturing Example 3. Introduction of a substituent in the α / β form to an arabinose derivative having a protecting group.

[0327]

[0328] Compound 73 (0.181 mmol), b (2 equivalents) was added to anhydrous DCM (3.6 mL) in the presence of argon and then cooled to -20 o TMSOTf (0.2 equiv) was added dropwise to C and stirred at room temperature overnight. Et3N was added dropwise to the mixture and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 20-33% EtOAc in hexane) to give compounds 71 ​​and 72.

[0329] Manufacturing Example 4. Introduction of a substituent in the α-form to an arabinose derivative having a protecting group.

[0330]

[0331] To a stirred solution of b (0.783 mmol) and compound 74 (1.174 mmol, 1.5 equiv) in THF (7.8 mL) were added triphenylphosphine (1.174 mmol, 1.5 equiv) and DEAD (1.174 mmol, 1.5 equiv) at 0 °C, and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (100-200 silica gel, 100 g, 25% EtOAc in Hexane) to obtain compound 72.

[0332] Manufacturing Example 5. Hydrolysis reaction using sodium methoxide

[0333]

[0334] Under argon conditions, compound 71 or 72 was mixed with 10 ml of methanol and then 0 o While stirring at C, slowly add 1.2 equivalents of sodium methoxide (5.4 M in MeOH) and raise the temperature to 25 o The reaction was carried out at C for 2 hours. After completion of the reaction, 10% HCl-methanol solution was slowly added dropwise to neutralize, and the residue was concentrated under reduced pressure. Then, the residue was purified by column chromatography (100-200 silica gel, 100 g, 5% MeOH in CH2Cl2) to obtain hydrolyzed compounds 75 or 76.

[0335] Manufacturing Example 6. Synthesis of (2R,3R,4S,5S)-2-(4-(5-methoxy-1H-indol-1-yl)phenoxy)tetrahyd ro-2H-pyran-3,4,5-triol

[0336] Step 1-1 C-N bond formation reaction of the Ullmann type

[0337]

[0338] CuI (0.08 mmol, 0.1 equiv), 2-(2-Pyridyl)benzimidazole (0.08 mmol, 0.1 equiv), and K3PO4 (1.6 mmol, 2 equiv) were added to DMF (10 mL), and the mixture was stirred at 50 °C after purging with argon gas. After 30 min, compound 77 (0.8 mmol) and compound 78 (1.2 mmol, 1.5 equiv) were added and stirred at 110 °C overnight. The mixture was filtered, and the filtrate was added with saturated NaHCO3 solution, and extracted with EA. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (EA:Hexane=1:6) to obtain compound 79.

[0339] Step 1-2 Suzuki coupling reaction

[0340]

[0341] K3PO4 (1.93 mmol, 2 equiv), compound 77 (0.96 mmol), compound 80 (1.16 mmol, 1.5 equiv), and Pd(dppf)Cl2 (0.067 mmol, 0.07 equiv) were added to DMF (8 mL), and the mixture was replaced with argon gas and stirred at 80°C overnight. Extraction was performed using a saturated aqueous solution of NaHCO3 and EA. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (EA:DCM=20-30%) to obtain compound 81.

[0342] Step 1-3 Debenzylation reaction

[0343]

[0344] Compound 79 (0.53 mmol) was dissolved in EtOH:EA = 1:2 (15 mL), and 10% Pd / C (wt 55%, 100 mg) was added. The mixture was replaced with hydrogen gas using a hydrogen balloon. After stirring overnight at room temperature, the mixture was filtered through Celite, concentrated under reduced pressure, and purified by column chromatography (MeOH:DCM = 5%) to obtain Example 82.

[0345] Manufacturing Example 7. Introduction of a substituent to the hydroxyl group of carbon 2 of compound 35

[0346] Step 1-1. Introduction of acetal protecting group to hydroxyl groups 3 and 4

[0347]

[0348] To a stirred solution of compound 75 or 76 in 5 mL of acetone, 2,2-dimethoxypropane (2 mmol) and para-toluenesulfonic acid hydrate (0.01 mmol) were added, and the mixture was stirred at room temperature for 21 h. Triethylamine (0.01 mmol) was added to the reaction mixture, and the mixture was stirred for 30 min. When the reaction was completed, the reaction mixture was concentrated under reduced pressure and purified by column chromatography (100-200 silica gel, 20 g, 20% EtOAc in Hexane) to obtain compound 82 or 83 as a white solid.

[0349] Step 1-2. Alkylation of the 2nd hydroxyl group

[0350]

[0351] To a stirred solution of compound 82 or 83 (0.466 mmol) in 4.7 mL of anhydrous DMF under an argon atmosphere, sodium hydride (0.932 mmol, 2 equivalents) was added at 0 °C and stirred for 1 h. Alkyl halide (0.932 mmol, 2 equivalents) was added dropwise and stirred at room temperature for 2 h. When the reaction was complete, 1.8 mL of water was added to the reaction mixture at 0 °C. After extraction with DCM (3.6 mL × 3), the mixture was washed with 3.6 mL of brine. The water was removed with Na2SO4, filtered, and concentrated under reduced pressure. The reaction mixture was purified by column chromatography (100-200 silica gel, 20 g, 20% EtOAc in Hexane) to give compound 84 or 85 as a colorless liquid.

[0352] Step 1-3. Deacetalization reaction

[0353]

[0354] To a stirred solution of compound 84 or 85 (0.440 mmol) in 4.4 mL of DCM was added 90% TFA (3.959 mmol, 10 equivalents) and stirred at room temperature for 2 h. When the reaction was complete, saturated aqueous sodium bicarbonate solution (4.0 mL) was added. After extraction with DCM (3.4 mL × 2), the mixture was washed with 3.4 mL of brine. Water was removed with Na2SO4, filtered, and concentrated under reduced pressure. The reaction mixture was purified by column chromatography (100-200 silica gel, 20 g, 50% EtOAc in hexane) to give compound 86 or 87 as a colorless liquid.

[0355] Manufacturing Example 8. Introduction of a substituent to the hydroxyl group of carbon 4 of compound No.

[0356] Step 1-1. Introduction of the 3,4-protecting group

[0357]

[0358] Under an argon atmosphere, compounds 75 or 76 (0.5 mmol) and 2,2,3,3-tetramethoxybutane (1.3 equiv.), CH(OMe)3 (4 equiv.), and CSA (10 mol%) were added to MeOH (6 mL) and stirred at 70 °C. When the reaction was complete, the solvent was concentrated under reduced pressure. The reaction mixture was purified by column chromatography (100-200 silica gel, 100 g, 5% MeOH in DCM) to obtain compounds 88 or 89.

[0359] Step 1-2. Alkylation of the 2nd hydroxyl group

[0360]

[0361] Under an argon atmosphere, NaH (2.5 eq) was added to a stirred solution of compound 88 or 89 (0.14 mmol) in anhydrous DCM (3 mL) at 0 °C and stirred for 10 min. Then, CH3I (2.0 eq) was added dropwise to the mixture and the mixture was reacted at room temperature for 3 h. When the reaction was completed, the organic layer was washed with a saturated brine solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified with (100-200 silica gel, 100 g, 25% EtOAc in hexane) to obtain compound 90 or 91.

[0362] Step 1-3. Compound deprotection reaction

[0363]

[0364] The same method as steps 1-3 of manufacturing method 7 above was used.

[0365] Manufacturing Example 9. Introduction of a substituent to the hydroxyl group of carbon 3 of compound No. 1.

[0366]

[0367] Under an argon atmosphere, compounds 75 or 76 (0.4 mmol) and Bu2SnCl2 (10 mol%) were added to MeOH / DMF (10:1, 2.2 mL), followed by the addition of K2CO3 (1.5 equiv) and CH3I (2.0 equiv), and the mixture was stirred at 80 °C. When the reaction was complete, the solvent was concentrated under reduced pressure. The reaction mixture was purified by column chromatography (100-200 silica gel, 100 g, 10% MeOH in DCM) to obtain compounds 94 or 95.

[0368] Manufacturing Example 10. Synthesis of arabinose derivatives

[0369] Step 1-1 Synthesis of dihydropyran

[0370]

[0371] To a stirred solution of 96 (14.7 mmol) in anhydrous MeCN (150 ml) under argon, zinc powder (102.9 mmol) and ammonium chloride (102.9 mmol) were added dropwise sequentially, and the mixture was stirred at room temperature for 2 h. When the reaction was confirmed to be complete, the inorganic salt as a reaction byproduct and the excess zinc powder were filtered and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 33% EtOAc in hexane) to obtain compound 97.

[0372] Step 1 - Fluorination synthesis of 22-OH

[0373]

[0374] Compound 98 (0.7 mmol) was dissolved in DMF (5 mL) under argon. Selectfluor (1.7 equiv) and H2O (5 mL) were added and stirred at room temperature for 12 h. Extraction was performed with EA and water, and the organic layer was combined, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. This was dissolved again in anhydrous DCM (5 mL) with DMAP (0.9 equiv) and Et3N (2 equiv). Ac2O (1.5 equiv) was added dropwise at 0 °C, and the mixture was stirred at room temperature. The reaction mixture was dissolved in EA, washed with 1 N HCl, and extracted. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 30% EtOAc in hexane) to obtain compound 99.

[0375] Step 1-32-Nitroxy derivative synthesis

[0376]

[0377] Under argon, compound 100 (18.2 mmol) was added to anhydrous MeCN (70 ml) at -10 °C, and then cerium ammonium nitrate (55 mmol) and sodium azide (36.4 mmol) were slowly added dropwise. The mixture was stirred at -10 °C for 8 hours. When the reaction was confirmed to be complete, the mixture was diluted with cold EtOAc (50 ml) and distilled water (50 ml), filtered using Celite, and the filtrate was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 40% EtOAc in hexane) to obtain compound 101.

[0378] Step 1-42-Acetyl derivative synthesis

[0379]

[0380] Compound 101 (4.5 mmol) and sodium acetate (8 mmol) were suspended in acetic acid (10 ml) and stirred at 100 °C for 1 h. When the reaction was complete, the mixture was diluted with DCM, washed with distilled water, a saturated aqueous sodium bicarbonate solution, and a saturated brine solution, and the organic layer was extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100-200 silica gel, 100 g, 40% EtOAc in hexane) to obtain compound 102.

[0381] Example 1. Preparation of (2R,3R,4S,5S)-2-(4-benzylphenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0382]

[0383] The above compound was synthesized through Manufacturing Examples 2 and 3, and the target compound was obtained by hydrolysis according to Manufacturing Example 5 after introduction of a substituent in the α / β form.

[0384] 1 H NMR (400 MHz, DMSO-d6) δ 7.27 (t,J= 7.4 Hz, 2H), 7.23 - 7.15 (m, 3H), 7.13 (d,J= 8.4 Hz, 2H), 6.95 (d,J= 8.5 Hz, 2H), 5.38 (s, 1H), 4.96 (s, 1H), 4.84 (s, 1H), 4.72 (s, 1H), 3.87 (s, 2H), 3.76 (s, 3H), 3.67 (d,J= 11.9 Hz, 1H), 3.48 (d,J= 10.8 Hz, 1H).

[0385] Example 2. Preparation of (2R,3R,4S,5S)-2-(4-(4-methylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0386]

[0387] Example 2 was able to obtain the target compound using the same method as Example 1.

[0388] 1 H NMR (400 MHz, CD3OD) δ 7.04 (dt,J= 21.1, 8.7 Hz, 8H), 5.46 (d,J= 3.2 Hz, 1H), 3.99 - 3.87 (m, 4H), 3.84 (s, 2H), 3.63 (d,J= 10.4 Hz, 1H), 2.27 (s, 3H).

[0389] Example 3. Preparation of (2R,3R,4S,5S)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0390]

[0391] Example 3 was able to obtain the target compound using the same method as Example 1.

[0392] 1 H NMR (400 MHz, DMSO-d6) δ 7.11 (dd,J= 8.4, 3.4 Hz, 4H), 6.94 (d,J= 8.5 Hz, 2H), 6.83 (d,J= 8.5 Hz, 2H), 5.37 (s, 1H), 4.89 (d,J= 5.3 Hz, 1H), 4.71 (d,J= 4.2 Hz, 1H), 4.63 (d,J= 3.2 Hz, 1H), 3.80 (s, 2H), 3.75 (s, 2H), 3.70 (s, 3H), 3.67 (d,J= 12.2 Hz, 1H), 3.47 (d,J= 11.9 Hz, 1H).

[0393] Example 4. Preparation of (2S,3R,4S,5S)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0394]

[0395] In the above Example 4, the target compound was obtained by hydrolyzing the compound b (synthesized using step 1 of Preparation Example 1) having a peracetyl-substituted arabinose and an alcohol substituent in accordance with Preparation Example 4, after introducing the substituent in the β form according to Preparation Example 4, according to Preparation Example 5.

[0396] 1 H NMR (400 MHz, DMSO-d6) δ 7.10 (d,J= 7.2 Hz, 4H), 6.91 (d,J= 8.2 Hz, 2H), 6.83 (d,J= 8.2 Hz, 2H), 5.18 (d,J= 4.9 Hz, 1H), 4.81 (d,J= 5.5 Hz, 1H), 4.77 (d,J= 6.9 Hz, 1H), 4.63 (d,J= 4.0 Hz, 1H), 3.80 (s, 2H), 3.71 - 3.67 (m, 4H), 3.54 (d,J= 11.5 Hz, 1H).

[0397] Example 5. Preparation of (3S,4S,5R,6R)-5-methoxy-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0398]

[0399] In the above Example 5, a compound having a peracetyl-substituted arabinose and an alcohol substituent was prepared by introducing a substituent in the α / β form in Preparation Example 2, and then going through steps 1-1 to 1-3 of Preparation Example 7 to obtain the target compound.

[0400] 1 H NMR (400 MHz, CD3OD) δ 7.10 (dd,J= 8.5, 3.7 Hz, 4H), 7.02 (d,J= 8.6 Hz, 2H), 6.83 (d,J= 8.5 Hz, 2H), 5.69 (d,J= 3.2 Hz, 1H), 4.18 (d,J= 9.6 Hz, 1H), 4.07 (s, 1H), 3.93 - 3.86 (m, 3H), 3.81 - 3.75 (m, 4H), 3.69 (dd,J= 9.7, 3.3 Hz, 1H), 3.49 (s, 3H), 2.68 (s, 1H), 2.60 (s, 1H).

[0401] Example 6. Preparation of (2R,3S,4R,5S,6S)-2-(4-(4-methoxybenzyl)phenoxy)-6-methyltetrahydro-2H-pyran-3,4,5-triol

[0402]

[0403] Example 6 was able to obtain the target compound using the same method as Example 1.

[0404] 1 H NMR (400 MHz, CD3OD) δ 7.08 (dd,J= 8.6, 3.4 Hz, 4H), 7.01 (d,J= 8.6 Hz, 2H), 6.81 (d,J= 8.6 Hz, 2H), 5.40 (d,J= 3.5 Hz, 1H), 3.96 - 3.91 (m, 1H), 3.87 (dd,J= 10.3, 3.8 Hz, 1H), 3.83 (s, 2H), 3.75 (s, 3H), 3.72 (s, 1H), 1.17 (d,J= 6.6 Hz, 3H).

[0405] Example 7. Preparation of (2R,3R,4S,5S)-2-(4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0406]

[0407] Example 7 was able to obtain the target compound using the same method as Example 1.

[0408] 1 H NMR (400 MHz, DMSO-d6) δ 7.12 (d,J= 3.3 Hz, 6H), 6.94 (d,J= 8.6 Hz, 2H), 5.37 (s, 1H), 4.90 (d,J= 5.5 Hz, 1H), 4.73 (d,J= 3.8 Hz, 1H), 4.65 (d,J= 3.3 Hz, 1H), 3.82 (s, 2H), 3.75 (s, 3H), 3.67 (d,J= 11.6 Hz, 1H), 3.47 (d,J= 10.9 Hz, 1H), 2.85 - 2.80 (m, 1H), 1.16 (d,J= 6.9 Hz, 6H).

[0409] Example 8. Preparation of (2R,3R,4S,5S)-2-(2-chloro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0410]

[0411] Example 8 was able to obtain the target compound using the same method as Example 1.

[0412] 1 H NMR (400 MHz, DMSO-d6) δ 7.27 (d,J= 1.5 Hz, 1H), 7.20 - 7.11 (m, 6H), 5.58 (d,J= 1.6 Hz, 1H), 4.97 (d,J= 4.8 Hz, 1H), 4.83 (d,J= 4.7 Hz, 1H), 4.67 (d,J= 3.4 Hz, 1H), 3.83 (s, 4H), 3.78 (s, 1H), 3.69 (d,J= 12.0 Hz, 1H), 3.50 - 3.44 (m, 1H), 2.83 (dt,J= 13.7, 6.9 Hz, 1H), 1.17 (s, 3H), 1.16 (s, 3H).

[0413] Example 9. Preparation of (2R,3R,4S,5S)-2-(4-(4-phenoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0414]

[0415] Example 9 was able to obtain the target compound using the same method as Example 1.

[0416] 1H NMR (400 MHz, DMSO-d6) δ 7.36 (dd,J= 8.3, 7.7 Hz, 2H), 7.22 (d,J= 8.4 Hz, 2H), 7.15 (d,J= 8.5 Hz, 2H), 7.10 (t,J= 7.4 Hz, 1H), 6.94 (dd,J= 14.4, 8.2 Hz, 6H), 5.39 (s, 1H), 4.89 (d,J= 5.3 Hz, 1H), 4.72 (d,J= 4.5 Hz, 1H), 4.64 (d,J= 3.3 Hz, 1H), 3.86 (s, 2H), 3.76 (s, 3H), 3.68 (d,J= 12.0 Hz, 1H), 3.48 (dd,J= 11.9, 1.9 Hz, 1H).

[0417] Example 10. Preparation of (2R,3R,4S,5S)-2-(4-(4-trifluoromethoxy)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0418]

[0419] Example 10 was able to obtain the target compound using the same method as Example 1.

[0420] 1 H NMR (400 MHz, DMSO-d6) δ 7.85 (d,J= 8.6 Hz, 2H), 7.76 (d,J= 8.7 Hz, 2H), 7.54 (d,J= 8.2 Hz, 2H), 7.20 (d,J= 8.7 Hz, 2H), 5.62 (s, 1H), 5.05 (d,J= 4.4 Hz, 1H), 4.81 (d,J= 0.9 Hz, 1H), 4.72 (d,J= 3.0 Hz, 1H), 3.82 (s, 2H), 3.67 (d,J= 11.7 Hz, 1H), 3.54 (dd,J= 11.8, 1.4 Hz, 1H).

[0421] Example 11. Preparation of (2R,3R,4S,5S)-2-(4-(4-(methylthio)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0422]

[0423] Example 11 was able to obtain the target compound using the same method as Example 1.

[0424] 1 H NMR (400 MHz, DMSO-d6) δ 7.16 (q,J= 8.5 Hz, 4H), 7.12 (d,J= 8.4 Hz, 2H), 6.94 (d,J= 8.4 Hz, 2H), 5.38 (s, 1H), 4.90 (d,J= 3.5 Hz, 1H), 4.73 (s, 1H), 4.65 (s, 1H), 3.82 (s, 2H), 3.75 (s, 3H), 3.67 (d,J= 11.9 Hz, 1H), 3.47 (d,J= 11.0 Hz, 1H), 2.43 (s, 3H).

[0425] Example 12. Preparation of (2S,3R,4S,5S)-2-(4-(4-(dimethylamino)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0426]

[0427] Example 12 was able to obtain the target compound using the same method as Example 4.

[0428] 1 H NMR (400 MHz, CD3OD) δ 7.03 (dd,J= 24.6, 8.5 Hz, 4H), 6.96 (d,J= 8.6 Hz, 2H), 6.72 (d,J= 8.6 Hz, 2H), 4.78 (d,J= 7.2 Hz, 1H), 3.90 (dd,J= 12.4, 2.5 Hz, 1H), 3.85 (s, 1H), 3.77 (d,J= 7.3 Hz, 1H), 3.66 (d,J= 12.3 Hz, 1H), 3.60 (dd,J= 9.1, 3.4 Hz, 1H), 2.86 (s, 6H).

[0429] Example 13. Preparation of (2R,3R,4S,5S)-2-(4-(4-fluorobenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0430]

[0431] Example 13 was able to obtain the target compound using the same method as Example 1.

[0432] 1 H NMR (400 MHz, CD3OD) δ 7.16 (dd,J= 8.2, 5.6 Hz, 2H), 7.10 (d,J= 8.5 Hz, 2H), 7.02 (d,J= 8.6 Hz, 2H), 6.97 (t,J= 8.8 Hz, 2H), 5.46 (d,J= 3.1 Hz, 1H), 3.99 - 3.87 (m, 6H), 3.63 (d,J= 11.0 Hz, 1H).

[0433] Example 14. Preparation of (2R,3R,4S,5S)-2-(4-(4-chlorobenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0434]

[0435] Example 14 was able to obtain the target compound using the same method as Example 1.

[0436] 1 H NMR (400 MHz, DMSO-d6) δ 7.33 (d,J= 8.3 Hz, 2H), 7.23 (d,J= 8.3 Hz, 2H), 7.13 (d,J= 8.5 Hz, 2H), 6.95 (d,J= 8.5 Hz, 2H), 5.38 (s, 1H), 4.89 (d,J= 4.6 Hz, 1H), 4.72 (d,J= 2.8 Hz, 1H), 4.64 (d,J= 2.5 Hz, 1H), 3.87 (s, 2H), 3.76 (s, 3H), 3.67 (d,J= 11.9 Hz, 1H), 3.48 (dd,J= 11.8, 1.4 Hz, 1H).

[0437] Example 15. Preparation of (2R,3R,4S,5S)-2-(4-(3-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0438]

[0439] Example 15 was able to obtain the target compound using the same method as Example 1.

[0440] 1 H NMR (400 MHz, CD3OD) δ 7.18 - 7.13 (m, 1H), 7.10 (d,J= 8.6 Hz, 2H), 7.02 (d,J= 8.6 Hz, 2H), 6.77 - 6.67 (m, 3H), 5.46 (d,J= 3.2 Hz, 1H), 3.99 - 3.88 (m, 4H), 3.86 (s, 2H), 3.73 (s, 3H), 3.63 (d,J= 10.3 Hz, 1H).

[0441] Example 16. Preparation of (2R,3R,4S,5S)-2-(4-(3,5-bis(trifluoromethyl)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0442]

[0443] Example 16 was able to obtain the target compound using the same method as Example 1.

[0444] 1 H NMR (400 MHz, DMSO-d6) δ 7.97 (s, 2H), 7.92 (s, 1H), 7.23 (d,J= 8.4 Hz, 2H), 6.99 (d,J= 8.5 Hz, 2H), 5.41 (s, 1H), 4.91 (s, 1H), 4.79 - 4.61 (m, 2H), 4.11 (s, 2H), 3.76 (s, 3H), 3.67 (d,J= 11.7 Hz, 1H), 3.48 (d,J= 11.4 Hz, 1H).

[0445] Example 17. Preparation of (2R,3R,4S,5S)-2-(4-(3,4-dimethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-triol

[0446]

[0447] Example 17 was able to obtain the target compound using the same method as Example 1.

[0448] 1 H NMR (400 MHz, CD3OD) δ 7.10 (d,J= 7.9 Hz, 2H), 7.02 (d,J= 7.0 Hz, 2H), 6.84 (d,J= 7.8 Hz, 1H), 6.76 (s, 1H), 6.71 (d,J= 7.6 Hz, 1H), 5.46 (s, 1H), 3.96 - 3.87 (m,J= 17.5, 9.9 Hz, 4H), 3.84 (s, 2H), 3.77 (d,J= 10.5 Hz, 6H), 3.63 (d,J= 11.9 Hz, 1H).

[0449] Example 18. Preparation of (2R,3R,4S,5S)-2-(4-(3,4,5-trimethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0450]

[0451] Example 18 was able to obtain the target compound using the same method as Example 1.

[0452] 1 H NMR (400 MHz, CD3OD) δ 7.13 (d,J= 8.4 Hz, 2H), 7.03 (d,J= 8.5 Hz, 2H), 6.48 (s, 2H), 5.47 (d,J= 2.9 Hz, 1H), 3.96 - 3.88 (m, 4H), 3.85 (s, 2H), 3.77 (s, 6H), 3.72 (s, 3H), 3.63 (d,J= 10.9 Hz, 1H).

[0453] Example 19. Preparation of (2R,3R,4S,5S)-2-(4-(naphthalen-2-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0454]

[0455] Example 19 was able to obtain the target compound using the same method as Example 1.

[0456] 1H NMR (400 MHz, DMSO-d6) δ 7.84 (dd,J= 12.7, 7.7 Hz, 3H), 7.72 (s, 1H), 7.46 (dt,J= 12.7, 6.2 Hz, 2H), 7.37 (d,J= 8.4 Hz, 1H), 7.19 (d,J= 8.5 Hz, 2H), 6.96 (d,J= 8.4 Hz, 2H), 5.38 (s, 1H), 4.92 (s, 1H), 4.77 (s, 1H), 4.67 (s, 1H), 4.04 (s, 2H), 3.76 (s, 3H), 3.67 (d,J=12.0 Hz, 1H), 3.47 (d,J= 9.9 Hz, 1H).

[0457] Example 20. Preparation of (2R,3R,4S,5S)-2-(4-(6-methoxynaphthalen-2-yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0458]

[0459] Example 20 was able to obtain the target compound using the same method as Example 1.

[0460] 1 H NMR (400 MHz, DMSO-d6) δ 7.75 (t,J= 7.9 Hz, 2H), 7.65 (s, 1H), 7.32 (d,J= 8.6 Hz, 1H), 7.26 (s, 1H), 7.20 (d,J= 8.4 Hz, 2H), 7.13 (dd,J= 8.9, 2.1 Hz, 1H), 6.97 (d,J= 8.4 Hz, 2H), 5.40 (d,J= 2.4 Hz, 1H), 4.00 (s, 2H), 3.85 (s, 3H), 3.82 - 3.77 (m, 6H), 3.69 (d,J=11.9 Hz, 1H), 3.49 (d,J= 10.6 Hz, 1H).

[0461] Example 21. Preparation of (2R,3R,4S,5S)-2-(4-(cyclopentylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0462]

[0463] Example 21 was able to obtain the target compound using the same method as Example 1.

[0464] 1 H NMR (400 MHz, DMSO-d6) δ 7.08 (d,J= 8.4 Hz, 2H), 6.92 (d,J= 8.5 Hz, 2H), 5.37 (d,J= 1.7 Hz, 1H), 4.90 (d,J= 4.1 Hz, 1H), 4.73 (s, 1H), 4.65 (s, 1H), 3.76 (s, 3H), 3.69 (d,J= 12.0 Hz, 1H), 3.49 (dd,J= 11.6, 1.7 Hz, 1H), 2.48 (s, 2H), 2.05 - 1.98 (m, 1H), 1.65 - 1.55 (m, 4H), 1.51 - 1.43 (m, 2H), 1.18 - 1.10 (m, 2H).

[0465] Example 22. Preparation of (2R,3R,4S,5S)-2-(4-(cyclohexylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0466]

[0467] Example 22 was able to obtain the target compound using the same method as Example 1.

[0468] 1 H NMR (400 MHz, CD3OD) δ 7.02 (q,J= 8.5 Hz, 4H), 5.46 (d,J= 3.2 Hz, 1H), 3.99 - 3.90 (m, 4H), 3.64 (d,J= 10.6 Hz, 1H), 2.42 (d,J= 7.1 Hz, 2H), 1.72 - 1.61 (m,J= 12.1 Hz, 5H), 1.50 - 1.44 (m, 1H), 1.25 - 1.16 (m, 3H), 0.99 - 0.87 (m,J= 11.5 Hz, 2H).

[0469] Example 23. Preparation of (2R,3R,4S,5S)-2-(4-(thiophen-3-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0470]

[0471] Example 23 was able to obtain the target compound using the same method as Example 1.

[0472] 1 H NMR (400 MHz, DMSO-d6) δ 7.31 (dd,J= 5.1, 1.0 Hz, 1H), 7.17 (d,J= 8.4 Hz, 2H), 6.97 (d,J= 8.5 Hz, 2H), 6.93 (dd,J= 5.0, 3.5 Hz, 1H), 6.87 (d,J= 2.3 Hz, 1H), 5.40 (s, 1H), 4.91 (s, 1H), 4.69 (d,J= 27.1 Hz, 2H), 4.07 (s, 2H), 3.76 (s, 3H), 3.68 (d,J= 11.8 Hz, 1H), 3.48 (dd,J= 11.8, 1.3 Hz, 1H).

[0473] Example 24. Preparation of (2S,3R,4S,5S)-2-(4-(pyridin-3-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0474]

[0475] Example 24 was able to obtain the target compound using the same method as Example 4.

[0476] 1H NMR (400 MHz, CD3OD) δ 8.40 (s, 1H), 8.35 (d,J= 4.3 Hz, 1H), 7.65 (d,J= 7.8 Hz, 1H), 7.34 (dd,J= 7.7, 5.0 Hz, 1H), 7.14 (d,J= 8.4 Hz, 2H), 7.02 (d,J= 8.5 Hz, 2H), 4.83 - 4.81 (d,J= 7.1 Hz, 1H), 3.97 (s, 2H), 3.94 - 3.86 (m,J= 17.6, 5.2 Hz, 2H), 3.83 - 3.77 (m, 1H), 3.68 (d,J= 11.8 Hz, 1H), 3.62 (dd,J= 9.0, 3.3 Hz, 1H).

[0477] Example 25. Preparation of (2R,3R,4S,5S)-2-(3-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0478]

[0479] Example 25 was able to obtain the target compound using the same method as Example 1.

[0480] 1 H NMR (400 MHz, DMSO-d6) δ 7.18 (dd,J= 8.8, 7.5 Hz, 1H), 7.13 (d,J= 8.6 Hz, 2H), 6.84 (m, 5H), 5.39 (s, 1H), 4.90 (d,J= 4.9 Hz, 1H), 4.72 (d,J= 3.5 Hz, 1H), 4.64 (d,J= 3.3 Hz, 1H), 3.83 (s, 2H), 3.75 (s, 3H), 3.71 (s, 3H), 3.66 (d,J= 12.1 Hz, 1H), 3.48 (dd,J= 12.0, 1.9 Hz, 1H).

[0481] Example 26. Preparation of (2R,3R,4S,5S)-2-((4-benzylphenyl)thio)tetrahydro-2H-pyran-3,4,5-thiol

[0482]

[0483] Example 26 was able to obtain the target compound using the same method as Example 1.

[0484] 1 H NMR (400 MHz, DMSO-d6) δ 7.29 (dd,J= 14.1, 7.7 Hz, 4H), 7.20 (dd,J= 18.0, 7.6 Hz, 5H), 5.34 (d,J= 5.5 Hz, 1H), 5.26 (d,J= 3.1 Hz, 1H), 4.88 (d,J= 4.5 Hz, 1H), 4.62 (d,J= 5.2 Hz, 1H), 3.90 (s, 2H), 3.78 (dd,J= 22.4, 10.2 Hz, 3H), 3.59 (s, 1H), 3.46 (dd,J= 10.8, 6.4 Hz, 1H).

[0485] Example 27. Preparation of (2R,3R,4S,5S)-2-((4-(4-isopropylbenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triol

[0486]

[0487] Example 27 was able to obtain the target compound using the same method as Example 1.

[0488] 1 H NMR (400 MHz, DMSO-d6) δ 7.28 (d,J= 7.9 Hz, 2H), 7.17 - 7.07 (m, 6H), 5.31 (d,J= 5.5 Hz, 1H), 5.23 (d,J= 3.2 Hz, 1H), 4.86 (d,J= 4.5 Hz, 1H), 4.60 (d,J= 5.1 Hz, 1H), 3.85 - 3.70 (m, 5H), 3.57 (s, 1H), 3.44 (dd,J= 11.0, 6.4 Hz, 1H), 2.84 - 2.77 (m, 1H), 1.14 (d,J=6.9 Hz, 6H).

[0489] Example 28. Preparation of (2S,3R,4S,5S)-2-((4-(4-isopropylbenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triol

[0490]

[0491] Example 28 was able to obtain the target compound using the same method as Example 1.

[0492] 1 H NMR (400 MHz, DMSO-d6) δ 7.30 (d,J= 8.0 Hz, 2H), 7.15 - 7.09 (m, 6H), 5.18 (d,J= 5.2 Hz, 1H), 4.85 (d,J= 4.8 Hz, 1H), 4.72 (d,J= 6.1 Hz, 1H), 4.58 (d,J= 5.0 Hz, 1H), 3.87 - 3.76 (m, 3H), 3.70 - 3.68 (m, 1H), 3.57 (q,J= 6.1 Hz, 1H), 3.48 - 3.44 (m, 1H), 3.39 (dd,J= 11.4, 2.7 Hz, 1H), 2.84 - 2.77 (m, 1H), 1.14 (d,J= 6.9 Hz, 6H).

[0493] Example 29. Preparation of (2R,3R,4S,5S)-2-((4-(4-methoxybenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-thiol

[0494]

[0495] Example 29 was able to obtain the target compound using the same method as Example 1.

[0496] 1 H NMR (400 MHz, DMSO-d6) δ 7.32 - 7.25 (m, 2H), 7.11 (dd,J= 11.1, 4.7 Hz, 4H), 6.87 - 6.78 (m, 2H), 5.34 (d,J= 5.5 Hz, 1H), 5.23 (d,J= 3.2 Hz, 1H), 4.88 (d,J= 4.5 Hz, 1H), 4.62 (d,J= 5.2 Hz, 1H), 3.83 - 3.71 (m, 5H), 3.68 (s, 3H), 3.57 (dt,J= 6.8, 3.6 Hz, 1H), 3.46 - 3.42 (m, 1H).

[0497] Example 30. Preparation of (2R,3R,4S,5S)-2-(4-(2-(4-methoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0498]

[0499] Example 30 was able to obtain the target compound using the same method as Example 1.

[0500] 1 H NMR (400 MHz, CD3OD) δ 7.12 (dd,J= 8.8, 4.6 Hz, 4H), 6.99 (d,J= 8.8 Hz, 2H), 6.79 (d,J= 8.8 Hz, 2H), 5.47 (d,J= 3.1 Hz, 1H), 3.94 (m,J= 20.7, 13.8, 7.5 Hz, 4H), 3.75 (s, 3H), 3.64 (s, 1H), 1.61 (s, 6H).

[0501] Example 31. Preparation of (2R,3R,4S,5S)-2-(4-(2-(4-ethoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0502]

[0503] Example 31 was able to obtain the target compound using the same method as Example 1.

[0504] 1 H NMR (400 MHz, CD3OD) δ 7.11 (dd,J= 10.9, 8.9 Hz, 4H), 6.98 (d,J= 8.8 Hz, 2H), 6.77 (d,J= 8.8 Hz, 2H), 5.47 (d,J= 3.2 Hz, 1H), 4.03 - 3.87 (m, 6H), 3.63 (d,J= 10.5 Hz, 1H), 1.61 (s, 6H), 1.35 (t,J= 7.0 Hz, 3H).

[0505] Example 32. Preparation of (2R,3R,4S,5S)-2-(4-(1,1,1,3,3,3-hexafluoro-2-(4-methoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0506]

[0507] Example 32 was able to obtain the target compound using the same method as Example 1.

[0508] 1 H NMR (400 MHz, DMSO-d6) δ 7.25 (d,J= 7.6 Hz, 4H), 7.13 (d,J= 9.0 Hz, 2H), 7.04 (d,J= 9.0 Hz, 2H), 5.52 (s, 1H), 4.98 (d,J= 4.3 Hz, 1H), 4.78 (d,J= 2.5 Hz, 1H), 4.70 (d,J= 3.4 Hz, 1H), 3.79 (d,J= 4.4 Hz, 6H), 3.68 (d,J= 11.8 Hz, 1H), 3.53 (dd,J= 11.9, 1.3 Hz, 1H).

[0509] Example 33. Preparation of (2R,3R,4S,5S)-2-(4-(para-tolyloxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0510]

[0511] Example 33 was able to obtain the target compound using the same method as Example 1.

[0512] 1H NMR (400 MHz, DMSO-d6) δ 7.15 (d,J= 8.1 Hz, 2H), 7.04 (d,J= 9.0 Hz, 2H), 6.93 (d,J= 9.0 Hz, 2H), 6.85 (d,J= 8.5 Hz, 2H), 5.37 (s, 1H), 4.92 (d,J= 5.6 Hz, 1H), 4.74 (d,J= 4.1 Hz, 1H), 4.66 (d,J= 3.4 Hz, 1H), 3.77 (s, 3H), 3.72 (d,J= 12.1 Hz, 1H), 3.51 (dd,J= 12.1, 1.9 Hz, 1H), 2.27 (s, 3H).

[0513] Example 34. Preparation of (2R,3R,4S,5S)-2-(4-(3,5-dimethylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0514]

[0515] Example 34 was able to obtain the target compound using the same method as Example 1.

[0516] 1 H NMR (400 MHz, DMSO-d6) δ 7.05 (d,J= 8.9 Hz, 2H), 6.94 (d,J= 8.9 Hz, 2H), 6.71 (s, 1H), 6.54 (s, 2H), 5.38 (s, 1H), 4.93 (d,J= 5.0 Hz, 1H), 4.75 (d,J= 3.1 Hz, 1H), 4.67 (d,J= 3.0 Hz, 1H), 3.77 (s, 3H), 3.72 (d,J= 11.7 Hz, 1H), 3.52 (dd,J= 11.0, 0.7 Hz, 1H), 2.22 (s, 6H).

[0517] Example 35. Preparation of (2R,3R,4S,5S)-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0518]

[0519] Example 35 was able to obtain the target compound using the same method as Example 1.

[0520] 1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d,J= 8.4 Hz, 2H), 7.05 (d,J= 8.9 Hz, 2H), 6.95 (d,J= 9.0 Hz, 2H), 6.87 (d,J= 8.5 Hz, 2H), 5.37 (s, 1H), 4.92 (d,J= 5.3 Hz, 1H), 4.74 (d,J= 3.4 Hz, 1H), 4.66 (d,J= 2.8 Hz, 1H), 3.77 (s, 3H), 3.72 (d,J= 11.9 Hz, 1H), 3.51 (dd,J= 11.9, 1.4 Hz, 1H), 2.89 - 2.84 (m, 1H), 1.19 (s, 3H), 1.17 (s, 3H).

[0521] Example 36. Preparation of (2R,3R,4S,5S)-2-(4-(4-(tert-butyl)phenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0522]

[0523] Example 36 was able to obtain the target compound using the same method as Example 1.

[0524] 1 H NMR (400 MHz, DMSO-d6) δ 7.36 (d,J= 8.8 Hz, 2H), 7.05 (d,J= 9.1 Hz, 2H), 6.95 (d,J= 9.0 Hz, 2H), 6.87 (d,J= 8.8 Hz, 2H), 5.38 (s, 1H), 4.93 (d,J= 5.5 Hz, 1H), 4.75 (d,J= 4.3 Hz, 1H), 4.67 (d,J= 3.2 Hz, 1H), 3.77 (s, 3H), 3.72 (d,J= 11.7 Hz, 1H), 3.51 (dd,J= 11.8, 2.1 Hz, 1H), 1.27 (s, 9H).

[0525] Example 37. Preparation of (2R,3R,4S,5S)-2-(4-(3-chloro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0526]

[0527] Example 37 was able to obtain the target compound using the same method as Example 1.

[0528] 1 H NMR (400 MHz, DMSO-d6) δ 7.25 (d,J= 1.7 Hz, 1H), 7.14 (m, 3H), 7.05 (d,J= 8.4 Hz, 1H), 6.95 (d,J= 8.5 Hz, 2H), 5.38 (s, 1H), 4.91 (d,J= 4.7 Hz, 1H), 4.74 (s, 1H), 4.66 (d,J= 3.0 Hz, 1H), 3.80 (s, 3H), 3.75 (s, 2H), 3.67 (d,J= 11.7 Hz, 1H), 3.47 (dd,J= 12.2, 1.7 Hz, 1H).

[0529] Example 38. Preparation of (2R,3R,4S,5S)-2-(3-chloro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0530]

[0531] Example 38 was able to obtain the target compound using the same method as Example 1.

[0532] 1 H NMR (400 MHz DMSO-d6) δ7.22 (d,J= 2.0 Hz, 1H), 7.18 - 7.05 (m, 4H), 6.87 - 6.77 (m, 2H), 5.57 (d,J= 2.5 Hz, 1H), 4.97 (d,J= 4.8 Hz, 1H), 4.83 (d,J= 4.7 Hz, 1H), 4.67 (d,J= 3.6 Hz, 1H), 3.84 - 3.60 (m, 9H), 3.45 (dd,J= 12.0, 2.2 Hz, 1H).

[0533] Example 39. Preparation of (2R,3R,4S,5S)-2-(4-(4-ethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0534]

[0535] Example 39 was able to obtain the target compound using the same method as Example 1.

[0536] 1 H NMR (400 MHz DMSO-d6) δ7.08 (dd,J= 8.5, 3.5 Hz, 4H), 6.92 (d,J= 8.5 Hz, 2H), 6.79 (d,J= 8.5 Hz, 2H), 5.35 (s, 1H), 4.89 (d,J= 5.3 Hz, 1H), 4.71 (d,J= 4.3 Hz, 1H), 4.63 (d,J= 3.3 Hz, 1H), 3.94 (q,J= 7.0 Hz, 2H), 3.77 (s, 2H), 3.73 (s, 3H), 3.65 (d,J= 11.9 Hz, 1H), 3.45 (d,J= 10.2 Hz, 1H), 1.27 (t,J= 7.0 Hz, 3H).

[0537] Example 40. Preparation of (2R,3R,4S,5S)-2-(3-chloro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0538]

[0539] Example 40 was able to obtain the target compound using the same method as Example 1.

[0540] 1H NMR (400 MHz DMSO-d6) δ7.08 (dd,J= 8.5, 3.5 Hz, 4H), 6.92 (d,J= 8.5 Hz, 2H), 6.79 (d,J= 8.5 Hz, 2H), 5.35 (s, 1H), 4.89 (d,J= 5.3 Hz, 1H), 4.71 (d,J= 4.3 Hz, 1H), 4.63 (d,J= 3.3 Hz, 1H), 3.94 (q,J= 7.0 Hz, 2H), 3.77 (s, 2H), 3.73 (s, 3H), 3.65 (d,J= 11.9 Hz, 1H), 3.45 (d,J= 10.2 Hz, 1H), 1.27 (t,J= 7.0 Hz, 3H).

[0541] Example 41. Preparation of (2R,3R,4S,5S)-2-(2-fluoro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0542]

[0543] Example 41 was able to obtain the target compound using the same method as Example 1.

[0544] 1 H NMR (400 MHz DMSO-d6) δ7.17 - 7.10 (m, 5H), 7.06 (dd,J= 12.2, 2.0 Hz, 1H), 6.94 (dd,J= 8.2, 2.0 Hz, 1H), 5.42 (d,J= 2.3 Hz, 1H), 4.98 (d,J= 4.6 Hz, 1H), 4.78 (d,J= 4.0 Hz, 1H), 4.66 (d,J= 3.4 Hz, 1H), 3.87 - 3.66 (m, 6H), 3.47 (dd,J= 12.0, 2.1 Hz, 1H), 2.84 - 2.77 (m, 1H), 1.14 (d,J= 6.9 Hz, 6H).

[0545] Example 42. Preparation of (2R,3R,4S,5R)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0546]

[0547] Example 42 was able to obtain the target compound using the same method as Example 1.

[0548] 1 H NMR (400 MHz DMSO-d6) δ7.11 (d,J= 7.0 Hz, 4H), 6.94 (d,J= 8.5 Hz, 2H), 6.83 (d,J= 8.6 Hz, 2H), 5.34 (d,J= 3.5 Hz, 1H), 5.03 (dd,J= 9.9, 5.4 Hz, 2H), 4.96 (d,J= 4.8 Hz, 1H), 3.80 (s, 2H), 3.70 (s, 3H), 3.57 - 3.51 (m, 1H), 3.46 (d,J= 4.8 Hz, 1H).

[0549] Example 43 Preparation of (2R,3R,4S,5R)-2-(4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0550]

[0551] Example 43 was able to obtain the target compound using the same method as Example 1.

[0552] 1 H NMR (400 MHz DMSO-d6) δ7.13 (m, 6H), 6.95 (d,J= 8.6 Hz, 2H), 5.34 (d,J= 3.5 Hz, 1H), 5.02 (dd,J= 10.2, 5.5 Hz, 2H), 4.95 (d,J= 4.5 Hz, 1H), 3.82 (s, 2H), 3.53 (s, 1H), 3.46 (d,J= 4.9 Hz, 1H), 2.85 - 2.79 (m, 1H), 1.17 (s, 3H), 1.15 (s, 3H).

[0553] Example 44 Preparation of (2R,3R,4S,5S)-2-(4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0554]

[0555] Example 44 was able to obtain the target compound using the same method as Example 1.

[0556] 1 H NMR (400 MHz DMSO-d6) δ7.08 (dd,J= 10.8, 8.6 Hz, 4H), 6.92 (d,J= 8.5 Hz, 2H), 6.78 (d,J= 8.5 Hz, 2H), 5.35 (s, 1H), 4.88 (d,J= 5.3 Hz, 1H), 4.71 (d,J= 4.3 Hz, 1H), 4.63 (d,J= 3.3 Hz, 1H), 4.51 (dt,J= 12.0, 6.0 Hz, 1H), 3.76 (s, 2H), 3.73 (s, 3H), 3.65 (d,J= 11.7 Hz, 1H), 3.45 (d,J= 10.7 Hz, 1H), 1.20 (d,J= 6.0 Hz, 6H).

[0557] Example 45 Preparation of (2R,3R,4S,5S)-2-(4-(4-(cyclopentyloxy)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0558]

[0559] Example 45 was able to obtain the target compound using the same method as Example 1.

[0560] 1 H NMR (400 MHz DMSO-d6) δ7.07 (dd,J= 11.5, 8.6 Hz, 4H), 6.92 (d,J= 8.5 Hz, 2H), 6.77 (d,J= 8.5 Hz, 2H), 5.35 (s, 1H), 4.88 (d,J= 5.3 Hz, 1H), 4.71 (d,J= 4.0 Hz, 1H), 4.63 (d,J= 3.2 Hz, 1H), 3.76 (s, 2H), 3.73 (s, 3H), 3.65 (d,J= 11.9 Hz, 1H), 3.45 (d,J= 10.0 Hz, 1H), 1.94 - 1.77 (m, 3H), 1.71 - 1.59 (m, 4H), 1.58 - 1.47 (m, 2H).

[0561] Example 46 Preparation of (2R,3R,4S,5S)-2-(2-fluoro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0562]

[0563] Example 46 was able to obtain the target compound using the same method as Example 1.

[0564] 1 H NMR (400 MHz, DMSO-d6) δ7.19 - 7.07 (m, 3H), 7.02 (dd,J= 12.3, 2.1 Hz, 1H), 6.92 (dd,J= 8.5, 2.1 Hz, 1H), 6.87 - 6.76 (m, 2H), 5.42 (d,J= 2.3 Hz, 1H), 4.99 (d,J= 4.9 Hz, 1H), 4.78 (d,J= 4.4 Hz, 1H), 4.66 (d,J= 3.4 Hz, 1H), 3.82 - 3.66 (m, 9H), 3.47 (dd,J= 12.0, 2.2 Hz, 1H).

[0565] Example 47 Preparation of (2R,3R,4S,5S)-2-(3-fluoro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0566]

[0567] Example 47 was able to obtain the target compound using the same method as Example 1.

[0568] 1H NMR (400 MHz, DMSO-d6) δ 7.15 (t,J= 8.7 Hz, 1H), 7.08 (d,J= 8.5 Hz, 2H), 6.88 - 6.76 (m, 4H), 5.42 (d,J= 2.1 Hz, 1H), 4.92 (dd,J= 4.3, 1.8 Hz, 1H), 4.73 (d,J= 4.5 Hz, 1H), 4.65 (d,J= 3.5 Hz, 1H), 3.81 - 3.62 (m, 9H), 3.47 (dd,J= 12.1, 2.2 Hz, 1H).

[0569] Example 48 Preparation of (2R,3R,4S,5S)-2-(3-fluoro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0570]

[0571] Example 48 was able to obtain the target compound using the same method as Example 1.

[0572] 1 H NMR (400 MHz, DMSO-d6) δ 7.18 (t,J= 8.7 Hz, 1H), 7.10 (q,J= 8.1 Hz, 4H), 6.85 - 6.79 (m, 2H), 5.42 (d,J= 2.1 Hz, 1H), 4.94 - 4.92 (m, 1H), 4.73 (d,J= 4.4 Hz, 1H), 4.66 (d,J= 3.5 Hz, 1H), 3.82 (s, 2H), 3.73 (dd,J= 4.1, 2.0 Hz, 3H), 3.63 (d,J= 12.0 Hz, 1H), 3.49 - 3.45 (m, 1H), 2.79 (h,J= 6.9 Hz, 1H), 1.14 (d,J= 6.9 Hz, 6H).

[0573] Example 49 Preparation of (2R,3R,4S,5S)-2-(4-(2-chloro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0574]

[0575] Example 49 was able to obtain the target compound using the same method as Example 1.

[0576] 1 H NMR (400 MHz, DMSO-d6) δ 7.25 (d,J= 1.8 Hz, 1H), 7.14 (m, 3H), 7.05 (d,J= 8.4 Hz, 1H), 6.95 (d,J= 8.5 Hz, 2H), 5.38 (d,J= 1.5 Hz, 1H), 4.89 (d,J= 5.5 Hz, 1H), 4.72 (d,J= 4.3 Hz, 1H), 4.64 (d,J= 3.4 Hz, 1H), 3.80 (s, 3H), 3.75 (s, 2H), 3.67 (d,J= 11.9 Hz, 1H), 3.47 (dd,J= 11.9, 1.8 Hz, 1H).

[0577] Example 50 Preparation of (2R,3R,4S,5S)-2-(4-(2-fluoro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0578]

[0579] Example 50 was able to obtain the target compound using the same method as Example 1.

[0580] 1 H NMR (400 MHz, DMSO-d6) δ 7.17 (t,J= 8.8 Hz, 1H), 7.09 (d,J= 8.4 Hz, 2H), 6.94 (d,J= 8.6 Hz, 2H), 6.78 (dd,J= 12.1, 2.4 Hz, 1H), 6.71 (dd,J= 8.4, 2.2 Hz, 1H), 5.37 (d,J= 1.5 Hz, 1H), 4.90 (d,J= 5.4 Hz, 1H), 4.73 (d,J= 4.2 Hz, 1H), 4.64 (d,J= 3.3 Hz, 1H), 3.81 (s, 2H), 3.75 (s, 3H), 3.66 (d,J= 12.0 Hz, 1H), 3.47 (dd,J= 11.8, 1.8 Hz, 1H).

[0581] Example 51 Preparation of (2R,3R,4S,5S)-2-(2-chloro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0582]

[0583] Example 51 was able to obtain the target compound using the same method as Example 1.

[0584] 1 H NMR (400 MHz, DMSO-d6) δ 7.24 (d,J= 2.0 Hz, 1H), 7.20 - 7.07 (m, 4H), 6.87 - 6.82 (m, 2H), 5.58 (d,J= 2.5 Hz, 1H), 4.98 (d,J= 4.7 Hz, 1H), 4.84 (d,J= 4.4 Hz, 1H), 4.68 (d,J= 3.7 Hz, 1H), 3.87 - 3.75 (m, 5H), 3.70 - 3.67 (m, 4H), 3.47 (dd,J= 12.1, 2.2 Hz, 1H).

[0585] Example 52 Preparation of (2R,3R,4S,5S)-2-(4-((4'-isopropyl-[1,1'-biphenyl]-4-yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0586]

[0587] Example 52 was able to obtain the target compound using the same method as Example 1.

[0588] 1H NMR (400 MHz, DMSO-d6) δ 7.52 (d,J= 7.0 Hz, 4H), 7.32 - 7.25 (m, 4H), 7.16 (d,J= 8.5 Hz, 2H), 6.95 (d,J= 8.6 Hz, 2H), 5.37 (s, 1H), 4.90 (d,J= 5.0 Hz, 1H), 4.73 (s, 1H), 4.65 (s, 1H), 3.89 (s, 2H), 3.74 (s, 3H), 3.66 (d,J= 11.5 Hz, 1H), 3.46 (d,J= 11.1 Hz, 1H), 2.95 - 2.85 (m, 1H), 1.21 (d,J= 6.9 Hz, 6H).

[0589] Example 53 Preparation of (2R,3R,4S,5S)-2-(4-((5-methoxybenzo[d]oxazol-2-yl)methol)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0590]

[0591] Example 53 was able to obtain the target compound using the same method as Example 1.

[0592] MS(m / z): 388.1 [M+H] +

[0593] Example 54 Preparation of (2R,3R,4S,5S)-2-(3-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0594]

[0595] Example 54 was able to obtain the target compound using the same method as Example 1.

[0596] 1H NMR (400 MHz, DMSO-d6) δ 7.28 - 7.23 (m, 3H), 6.96 (d,J= 8.6 Hz, 2H), 6.79 (dd,J= 8.4, 1.8 Hz, 1H), 6.61 (d,J= 2.2 Hz, 1H), 6.58 (dd,J= 8.2, 1.8 Hz, 1H), 5.40 (s, 1H), 4.93 (s, 1H), 4.75 (s, 1H), 4.66 (s, 1H), 3.74 (s, 3H), 3.66 (d,J= 11.8 Hz, 1H), 3.49 (dd,J= 12.0, 2.1 Hz, 1H), 2.92 - 2.87 (m, 1H), 1.21 (s, 3H), 1.19 (s, 3H).

[0597] Example 55 Preparation of (2R,3R,4S,5S)-2-(4-(4-methoxyphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0598]

[0599] Example 55 was able to obtain the target compound using the same method as Example 1.

[0600] 1 H NMR (400 MHz, DMSO-d6) δ 7.00 (d,J= 9.1 Hz, 2H), 6.93 - 6.83 (m, 6H), 5.33 (s, 1H), 4.91 (d,J= 5.5 Hz, 1H), 4.73 (d,J= 3.8 Hz, 1H), 4.65 (d,J= 3.2 Hz, 1H), 3.74 (d,J= 1.6 Hz, 3H), 3.71-3.68 (m, 4H), 3.48 (d,J= 11.8 Hz, 1H).

[0601] Example 56 Preparation of (2R,3R,4S,5R)-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0602]

[0603] Example 56 was able to obtain the target compound using the same method as Example 1.

[0604] 1 H NMR (400 MHz, DMSO-d6) δ 7.22 (d,J= 8.4 Hz, 2H), 7.05 (d,J= 9.1 Hz, 2H), 6.95 (d,J= 9.0 Hz, 2H), 6.87 (d,J= 8.6 Hz, 2H), 5.34 (d,J= 3.5 Hz, 1H), 5.07 (d,J= 6.4 Hz, 1H), 5.03 (d,J= 4.6 Hz, 1H), 4.97 (d,J= 5.0 Hz, 1H), 3.55 (dd,J= 8.4, 5.2 Hz, 1H), 3.50 (d,J= 5.0 Hz, 1H), 3.37 (d,J= 6.1 Hz, 3H), 2.85 (dd,J= 13.4, 6.6 Hz, 1H), 1.19 (s, 3H), 1.17 (s, 3H).

[0605] Example 57 Preparation of (2R,3R,4S,5S)-2-(2-chloro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0606]

[0607] Example 57 was able to obtain the target compound using the same method as Example 1.

[0608] 1 H NMR (400 MHz, DMSO-d6) δ 7.31 - 7.19 (m, 3H), 7.08 (d,J= 2.9 Hz, 1H), 6.94 - 6.89 (m, 3H), 5.55 (d,J= 2.3 Hz, 1H), 5.00 (d,J= 4.6 Hz, 1H), 4.85 (d,J= 4.4 Hz, 1H), 4.69 (d,J= 3.6 Hz, 1H), 3.85 - 3.69 (m, 4H), 3.49 (dd,J= 12.0, 2.2 Hz, 1H), 2.86 (hept,J= 6.9 Hz, 1H), 1.17 (d,J= 6.9 Hz, 6H).

[0609] Example 58 Preparation of (2R,3R,4R,5S)-5-fluoro-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0610]

[0611] Example 58 was able to obtain the target compound by additionally synthesizing a compound produced in the same manner as Example 1 using the method of Manufacturing Example 8.

[0612] 1 H NMR (400 MHz, DMSO-d6) δ 7.22 (d,J= 8.4 Hz, 2H), 7.07 (d,J= 9.0 Hz, 2H), 6.96 (d,J= 9.0 Hz, 2H), 6.87 (d,J= 8.6 Hz, 2H), 5.46 (d,J= 3.3 Hz, 1H), 5.25 (dd,J= 27.8, 5.7 Hz, 2H), 4.83 - 4.71 (d,J= 49.8 Hz, 1H), 3.96 - 3.70 (m, 5H), 2.86 (dt,J= 14.0, 7.1 Hz, 1H), 1.19 (s, 3H), 1.18 (s, 3H).

[0613] Example 59 Preparation of (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-(4-(4-isopropylphenoxy) phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0614]

[0615] Example 59 was able to obtain the target compound using the same method as Example 1.

[0616] 1H NMR (400 MHz, DMSO-d6) δ 7.21 (d,J= 8.4 Hz, 2H), 7.09 (d,J= 9.0 Hz, 2H), 6.94 (d,J= 9.0 Hz, 2H), 6.87 (d,J= 8.5 Hz, 2H), 5.31 (d,J= 2.1 Hz, 1H), 4.86 (d,J= 5.9 Hz, 1H), 4.73 (d,J= 4.8 Hz, 1H), 4.54 (t,J= 4.3 Hz, 2H), 3.76 (dd,J= 16.3, 4.6 Hz, 4H), 3.56 - 3.50 (m, 1H), 3.43 - 3.37 (m, 1H), 2.86 (dt,J= 13.9, 6.9 Hz, 1H), 1.19 (s, 3H), 1.17 (s, 3H).

[0617] Example 60 Preparation of (2R,3R,4S,5S)-2-(4-(4-isopropylphenoxy)phenoxy)-4-methoxytetrahydro-2H-pyran-3,5-diol

[0618]

[0619] Example 60 was able to obtain the target compound by additionally synthesizing a compound prepared in the same manner as Example 1 using the method of Manufacturing Example 9.

[0620] 1H NMR (400 MHz, DMSO-d6) δ 7.23 - 7.16 (m, 2H), 7.03 (td,J= 6.4, 2.2 Hz, 2H), 6.96 - 6.90 (m, 2H), 6.88 - 6.82 (m, 2H), 5.36 (d,J= 3.5 Hz, 1H), 5.01 (d,J= 6.8 Hz, 1H), 4.70 (d,J= 4.1 Hz, 1H), 3.99 (d,J= 4.5 Hz, 1H), 3.85 (ddd,J= 10.1, 6.7, 3.5 Hz, 1H), 3.70 (d,J= 12.0 Hz, 1H), 3.52 (dd,J= 12.1, 2.3 Hz, 1H), 3.36 (s, 3H), 3.44 (dd,J= 9.8, 3.2 Hz, 1H), 2.83 (h,J= 6.9 Hz, 1H), 1.16 (d,J= 6.9 Hz, 6H).

[0621] Example 61 Preparation of (2R,3R,4R,5S)-2-(4-(4-isopropylphenoxy)phenoxy)-5-methoxytetrahydro-2H-pyran-3,4-diol

[0622]

[0623] Example 61 was able to obtain the target compound by additionally synthesizing a compound prepared in the same manner as Example 1 using Manufacturing Example 7.

[0624] 1H NMR (400 MHz, DMSO-d6) δ 7.20 (d,J= 8.5 Hz, 2H), 7.05 - 7.01 (m, 2H), 6.95 - 6.90 (m, 2H), 6.87 - 6.82 (m, 2H), 5.35 (d,J= 3.4 Hz, 1H), 4.95 (d,J= 6.5 Hz, 1H), 4.75 (d,J= 6.1 Hz, 1H), 3.84 (ddd,J= 9.6, 6.2, 3.5 Hz, 1H), 3.74 - 3.67 (m, 2H), 3.61 (d,J= 12.2 Hz, 1H), 3.44 (s, 1H), 3.31 (s, 3H), 2.84 (p,J= 7.0 Hz, 1H), 1.16 (d,J= 6.9 Hz, 6H).

[0625] Example 62 Preparation of (3S,4S,5R,6R)-6-(4-(4-isopropylphenoxy)phenoxy)-5-methoxytetrahydro-2H-pyran-3,4-diol

[0626]

[0627] Example 62 was able to obtain the target compound by additionally synthesizing a compound prepared in the same manner as Example 1 using Manufacturing Example 7.

[0628] 1 H NMR (400 MHz, DMSO-d6) δ 7.22 (d,J= 8.5 Hz, 2H), 7.05 (d,J= 9.0 Hz, 2H), 6.95 (d,J= 9.0 Hz, 2H), 6.87 (d,J= 8.5 Hz, 2H), 5.66 (d,J= 3.2 Hz, 1H), 4.94 (d,J= 6.1 Hz, 1H), 4.78 (d,J= 3.6 Hz, 1H), 3.86 (ddd,J= 9.6, 6.2, 3.4 Hz, 1H), 3.76 (s, 1H), 3.70 (d,J= 11.9 Hz, 1H), 3.50 (d,J= 3.6 Hz, 2H), 3.41 (s, 3H), 2.86 (dt,J= 13.7, 6.9 Hz, 1H), 1.18 (d,J= 6.9 Hz, 6H).

[0629] Example 63 Preparation of (3S,4S,5R,6R)-5-fluoro-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0630]

[0631] Example 63 was able to obtain the target compound using the same method as Example 1 of Compound No. 99 of Example 10.

[0632] 1 H NMR (400 MHz, DMSO-d6) δ 7.22 (d,J= 8.5 Hz, 2H), 7.07 (t,J= 8.6 Hz, 2H), 6.97 (d,J= 8.8 Hz, 2H), 6.92 - 6.83 (m, 2H), 5.75 (s, 1H), 5.35 (dd,J= 23.1, 6.2 Hz, 1H), 5.03 - 4.96 (m, 1H), 4.77 - 4.58 (m, 1H), 4.57 - 4.33 (m, 1H), 3.75 (d,J= 6.3 Hz, 1H), 3.69 (d,J= 12.3 Hz, 1H), 3.55 (d,J= 12.3 Hz, 1H), 2.87 (dt,J= 13.6, 6.7 Hz, 1H), 1.19 (d,J= 6.9 Hz, 6H)

[0633] MS(m / z): 385.1 [M+Na] +

[0634] Example 64 Preparation of (2R,3R,4R,5R)-5-fluoro-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-di

[0635]

[0636] Example 64 was able to obtain the target compound using the same method as Example 58.

[0637] 1H NMR (400 MHz, DMSO-d6) δ 7.22 (d,J= 8.4 Hz, 2H), 7.09 (d,J= 9.0 Hz, 2H), 6.96 (d,J= 9.0 Hz, 2H), 6.88 (d,J= 8.6 Hz, 2H), 5.54 (d,J= 4.8 Hz, 1H), 5.40 (d,J= 3.6 Hz, 2H), 4.50 - 4.31 (m, 1H), 3.82 (dd,J= 10.7, 5.8 Hz, 2H), 3.58 (td,J= 10.7, 5.0 Hz, 1H), 3.46 - 3.41 (m, 1H), 2.89 - 2.84 (m, 1H), 1.19 (s, 3H), 1.18 (s, 3H).

[0638] Example 65 Preparation of (3S,4S,5S,6R)-5-fluoro-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0639]

[0640] Example 65 was able to obtain the target compound using the same method as Example 63.

[0641] 1 H NMR (400 MHz, DMSO-d6) δ 7.22 (d,J= 8.5 Hz, 2H), 7.05 (d,J= 9.0 Hz, 2H), 6.96 (d,J= 9.1 Hz, 2H), 6.88 (d,J= 8.6 Hz, 2H), 5.41 - 5.33 (m, 2H), 4.90 (d,J= 5.3 Hz, 1H), 4.49 (ddd,J= 48.1, 6.7, 2.9 Hz, 1H), 4.11 (dd,J= 14.7, 3.5 Hz, 1H), 3.72 - 3.60 (m, 3H), 2.87 (dt,J=14.1, 6.9 Hz, 1H), 1.19 (s, 3H), 1.18 (s, 3H).

[0642] Example 66 Preparation of (3S,4R,6R)-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0643]

[0644] Example 66 was able to obtain the target compound using the 100th compound of Example 10 using the same method as Example 1.

[0645] 1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d,J= 8.5 Hz, 2H), 7.03 (d,J= 9.0 Hz, 2H), 6.94 (d,J= 9.0 Hz, 2H), 6.86 (d,J= 8.6 Hz, 2H), 5.58 (t,J= 6.1 Hz, 1H), 4.74 (d,J= 5.5 Hz, 1H), 4.65 (d,J= 4.0 Hz, 1H), 3.97 (dd,J= 8.8, 5.0 Hz, 1H), 3.72 - 3.62 (m, 2H), 3.56 (dd,J= 11.6, 3.6 Hz, 1H), 2.86 (dt,J= 13.8, 7.0 Hz, 1H), 2.06 - 1.98 (m, 1H), 1.84 - 1.72 (m, 1H), 1.18 (d,J= 6.9 Hz, 6H).

[0646] MS(m / z): 367.2 [M+Na] +

[0647] Example 67 Preparation of (2R,3R,4S,5R)-2-(2-chloro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0648]

[0649] Example 67 was able to obtain the target compound using the same method as Example 1.

[0650] 1H NMR (400 MHz, DMSO-d6) δ 7.26 (t,J= 9.0 Hz, 3H), 7.11 (d,J= 2.9 Hz, 1H), 6.98 - 6.91 (m, 3H), 5.53 (d,J= 3.5 Hz, 1H), 5.17 (d,J= 5.6 Hz, 1H), 5.10 (d,J= 4.4 Hz, 1H), 5.07 (d,J= 4.9 Hz, 1H), 3.68 - 3.59 (m, 1H), 3.54 - 3.48 (m, 1H), 3.46 - 3.37 (m, 3H), 2.88 (p,J=6.9 Hz, 1H), 1.19 (d,J= 6.9 Hz, 6H).

[0651] Example 68 Preparation of (2R,3R,4S,5S)-2-(2-fluoro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0652]

[0653] Example 68 was able to obtain the target compound using the same method as Example 1.

[0654] 1 H NMR (400 MHz, DMSO-d6) δ 7.28 - 7.17 (m, 3H), 6.95 - 6.89 (m, 2H), 6.80 - 6.67 (m, 2H), 5.46 (d,J= 3.0 Hz, 1H), 4.09 - 3.92 (m, 4H), 3.67 (dd,J= 12.4, 2.1 Hz, 1H), 2.90 (hept,J= 6.9 Hz, 1H), 1.24 (d,J= 6.9 Hz, 6H).

[0655] Example 69 Preparation of (3S,4R,5R,6R)-5-azido-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0656]

[0657] Example 69 was able to obtain the target compound using the same method as Example 1, compound number 102 of Example 10.

[0658] 1 H NMR (400 MHz, DMSO-d6) δ 7.18 (d,J= 8.5 Hz, 2H), 7.07 (d,J= 9.0 Hz, 2H), 6.92 (d,J= 9.0 Hz, 2H), 6.85 (d,J= 8.6 Hz, 2H), 5.53 (d,J= 3.3 Hz, 1H), 4.19 (dd,J= 10.5, 3.2 Hz, 1H), 3.97 (d,J= 12.2 Hz, 2H), 3.73 - 3.61 (m, 2H), 2.86 (dq,J= 14.0, 6.9 Hz, 1H), 1.23 (d,J=6.9 Hz, 6H).

[0659] Example 70 Preparation of (3S,4R,5R,6R)-5-amino-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol

[0660]

[0661] Example 70: Pd / C (10%) was carefully added to a mixed solution of anhydrous EtOAc (10 ml) and Example 69 (1.0 mmol) under argon, stirred, and the interior of the reaction vessel was replaced with hydrogen gas. The reaction mixture was then stirred at 25°C for 1 hour. After completion of the reaction, the Pd / C catalyst was removed using a Celite filter and concentrated under reduced pressure. The reaction mixture was solidified with DCM / Hexane to obtain compound No. 70.

[0662] 1H NMR (400 MHz, DMSO-d6) δ 7.18 (d,J= 8.5 Hz, 2H), 7.10 (d,J= 9.0 Hz, 2H), 6.91 (d,J= 9.0 Hz, 2H), 6.84 (d,J= 8.6 Hz, 2H), 5.46 (d,J= 3.3 Hz, 1H), 3.96 (d,J= 12.5 Hz, 1H), 3.88 (s, 1H), 3.80 (dd,J= 10.1, 3.2 Hz, 1H), 3.69 (d,J= 12.5 Hz, 1H), 3.15 (dd,J= 10.2, 3.4 Hz, 1H), 2.87 (dt,J= 13.9, 6.8 Hz, 1H), 1.23 (d,J= 6.9 Hz, 6H).

[0663] Example 71 Preparation of (4-methoxyphenyl)(4-(((2R,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone

[0664]

[0665] Example 71 was able to obtain the target compound using the same method as Example 1.

[0666] 1 H NMR (400 MHz, DMSO-d6) δ 7.79 - 7.63 (m, 4H), 7.09 (dd,J= 23.2, 8.7 Hz, 4H), 5.27 (d,J= 5.1 Hz, 1H), 4.97 (d,J= 6.8 Hz, 1H), 4.86 (s, 1H), 4.67 (d,J= 4.1 Hz, 1H), 3.84 (s, 3H), 3.77 - 3.68 (m, 2H), 3.63 (d,J= 10.9 Hz, 2H), 3.50 - 3.43 (m, 1H).

[0667] Example 724 Preparation of (4-(((2S,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)benzoyl)benzonitrile

[0668]

[0669] Example 72 was synthesized through Manufacturing Example 3, and the target compound was obtained by hydrolysis according to Manufacturing Example 5 after introduction of a substituent in the α / β form.

[0670] 1 H NMR (400 MHz, DMSO-d6) δ 8.03 (d,J= 8.3 Hz, 2H), 7.84 (d,J= 8.3 Hz, 2H), 7.76 (d,J= 8.8 Hz, 2H), 7.17 (d,J= 8.9 Hz, 2H), 5.31 (d,J= 5.1 Hz, 1H), 5.02 (d,J= 6.7 Hz, 1H), 4.91 (d,J= 5.5 Hz, 1H), 4.71 (d,J= 3.8 Hz, 1H), 3.73 (dd,J= 11.6, 8.0 Hz, 2H), 3.65 (d,J= 10.9 Hz, 2H), 3.51 - 3.47 (m, 1H).

[0671] Example 73 Preparation of (2R,3R,4S,5S)-2-(4-(((1r,4R)-4-ethylcyclohexyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0672]

[0673] Example 73 was able to obtain the target compound using the same method as Example 1.

[0674] 1H NMR (400 MHz, DMSO-d6) δ 7.02 (d,J= 8.4 Hz, 2H), 6.90 (d,J= 8.5 Hz, 2H), 5.35 (s, 1H), 4.89 (d,J= 5.1 Hz, 1H), 4.72 (d,J= 4.0 Hz, 1H), 4.64 (d,J= 3.0 Hz, 1H), 3.74 (s, 3H), 3.67 (d,J= 11.8 Hz, 1H), 3.47 (d,J= 10.5 Hz, 1H), 2.36 (d,J= 6.9 Hz, 2H), 1.63 (dd,J= 24.2, 12.3 Hz, 4H), 1.39 - 1.30 (m, 1H), 1.20 - 1.08 (m, 2H), 1.02 (s, 1H), 0.95 - 0.68 (m, 7H).

[0675] Example 74 Preparation of (2R,3R,4S,5S)-2-(4-(((1r,4R)-4-isopropylcyclohexyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0676]

[0677] Example 74 was able to obtain the target compound using the same method as Example 1.

[0678] 1 H NMR (400 MHz, DMSO-d6) δ 7.02 (d,J= 8.4 Hz, 2H), 6.90 (d,J= 8.5 Hz, 2H), 5.35 (s, 1H), 4.89 (d,J= 5.4 Hz, 1H), 4.72 (d,J= 4.4 Hz, 1H), 4.64 (d,J= 3.2 Hz, 1H), 3.72 (d,J= 18.5 Hz, 3H), 3.67 (d,J= 12.0 Hz, 1H), 3.47 (d,J= 10.6 Hz, 1H), 2.35 (d,J= 7.0 Hz, 2H), 1.62 (s, 4H), 1.34 (dd,J= 12.4, 6.5 Hz, 2H), 0.87 (dd,J= 20.1, 11.2 Hz, 5H), 0.79 (d,J= 6.8 Hz, 6H).

[0679] Example 75 Preparation of (2S,3R,4S,5S)-2-(4-(pyrrolidin-1-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0680]

[0681] Example 75 was able to obtain the target compound using the same method as Example 1.

[0682] 1 H NMR (400 MHz, DMSO-d6) δ 7.26 (d,J= 8.5 Hz, 2H), 7.03 (d,J= 8.6 Hz, 2H), 4.83 (s, 1H), 3.92 (d,J= 12.5 Hz, 1H), 3.88 (s, 1H), 3.83 - 3.78 (m, 1H), 3.70 (d,J= 12.5 Hz, 1H), 3.63 (dd,J= 9.1, 3.4 Hz, 1H), 3.57 (s, 2H), 2.52 (s, 4H), 1.80 (s, 4H).

[0683] MS(m / z): 310.2 [M+Na] +

[0684] Example 76 Preparation of (2S,3R,4S,5S)-2-(4-(morpholinomethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0685]

[0686] Example 76 was able to obtain the target compound using the same method as Example 4.

[0687] 1 H NMR (400 MHz, DMSO-d6) δ%) 1H NMR (400 MHz, dmso) δ 7.20 (d,J= 8.5 Hz, 2H), 6.95 (d,J= 8.5 Hz, 2H), 5.22 (s, 1H), 4.89 (s, 1H), 4.80 (d,J= 6.9 Hz, 1H), 4.66 (s, 1H), 3.69 (d,J= 6.6 Hz, 2H), 3.56 (t,J= 8.4 Hz, 5H), 3.44 (d,J= 8.1 Hz, 1H), 3.38 (s, 2H), 3.17 (d,J= 4.3 Hz, 1H), 2.32 (s, 4H).

[0688] MS(m / z): 326.3 [M+Na] +

[0689] Example 77 Preparation of (3S,4R,5R,6R)-5-azido-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran)-3,4-diol

[0690]

[0691] Example 77 was able to obtain the target compound using the same method as Example 69.

[0692] 1 H NMR (400 MHz, DMSO-d6) δ 7.08 (t,J= 9.5 Hz, 4H), 6.99 (d,J= 8.6 Hz, 2H), 6.81 (d,J= 8.6 Hz, 2H), 5.53 (d,J= 3.4 Hz, 1H), 4.18 (dd,J= 10.5, 3.2 Hz, 1H), 3.97 - 3.90 (m, 2H), 3.84 (s, 2H), 3.74 (s, 3H), 3.64 (ddd,J= 13.8, 11.6, 2.8 Hz, 2H).

[0693] Example 78 Preparation of (3S,4R,5R,6R)-5-azido-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran)-3,4-diol

[0694]

[0695] Example 78 was able to obtain the target compound using the same method as Example 70.

[0696] 1 H NMR (400 MHz, DMSO-d6) δ 7.10 (t,J= 9.5 Hz, 4H), 7.01 (d,J= 8.6 Hz, 2H), 6.79 (d,J= 8.6 Hz, 2H), 5.46 (d,J= 3.4 Hz, 1H), 3.95 (dd,J= 10.5, 3.2 Hz, 1H), 3.88 - 3.80 (m, 2H), 3.77 (s, 2H), 3.74 (s, 3H), 3.34 (ddd,J= 13.8, 11.6, 2.8 Hz, 2H).

[0697] Example 79 Preparation of (2R,3R,4S,5S)-4,5-dihydroxy-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3-yl 10-aminodecanoate

[0698]

[0699] Example 79 was able to obtain the target compound using the same method as Example 62.

[0700] 1 H NMR (400 MHz, DMSO-d6) δ 7.08 (d,J= 8.1 Hz, 4H), 6.89 (d,J= 8.4 Hz, 2H), 6.84 - 6.77 (m, 2H), 5.52 (d,J= 3.5 Hz, 1H), 4.98 (dd,J= 10.1, 3.5 Hz, 1H), 3.96 (dd,J= 10.3, 3.3 Hz, 1H), 3.75 (q,J= 12.8 Hz, 4H), 3.68 (s, 3H), 3.51 (dd,J= 12.3, 2.1 Hz, 1H), 2.85 (q,J=6.6 Hz, 2H), 2.27 (t,J= 7.2 Hz, 2H), 1.52 - 1.42 (m, 2H), 1.36 - 1.27 (m, 6H), 1.15 - 1.11 (m, 8H).

[0701] MS(m / z): 516.2 [M+H]+

[0702] Example 80 Preparation of (2R,3R,4S,5S)-2-((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol

[0703]

[0704] Example 80 was able to obtain the target compound using the same method as Manufacturing Example 6.

[0705] 1 H NMR (400 MHz, DMSO-d6) δ 7.57 (d,J= 8.7 Hz, 2H), 7.32 (t,J= 7.8 Hz, 1H), 7.22 (d,J= 8.6 Hz, 2H), 7.03 - 6.93 (m, 3H), 5.52 (s, 1H), 4.93 (d,J= 5.0 Hz, 1H), 4.76 (s, 1H), 4.66 (s, 1H), 3.77 (bs, 6H), 3.72 (d,J= 12.0 Hz, 1H), 3.50 (d,J= 11.8 Hz, 1H).

[0706] Example 81 Preparation of (2R,3R,4S,5S)-2-(4-(6-methoxybenzofuran-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0707]

[0708] Example 81 was able to obtain the target compound using the same method as Example 1.

[0709] 1H NMR (400 MHz, DMSO-d6) δ 7.77 (d,J=8.8 Hz, 2H), 7.50 - 7.42 (m, 1H), 7.21 (s, 1H), 7.19 - 7.08 (m, 3H), 6.89 - 6.82 (m, 1H), 5.50 (s, 1H), 4.97 (s, 1H), 4.76 (s, 1H), 4.67 (s, 1H), 3.89 (s, 1H), 3.79 (bs, 5H), 3.68 (d,J= 11.7 Hz, 1H), 3.51 (d,J= 10.0 Hz, 1H).

[0710] Example 82 Preparation of (2R,3R,4S,5S)-2-(4-(5-methoxy-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0711]

[0712] Example 82 was able to obtain the target compound using the same method as Manufacturing Example 6.

[0713] 1 H NMR (400 MHz, DMSO-d6) δ 7.49 (d,J= 3.0 Hz, 1H), 7.45 (d,J= 8.8 Hz, 2H), 7.36 (d,J= 8.9 Hz, 1H), 7.21 (d,J= 8.8 Hz, 2H), 7.13 (d,J= 2.1 Hz, 1H), 6.80 (dd,J= 8.9, 2.3 Hz, 1H), 6.56 (d,J= 2.7 Hz, 1H), 5.50 (s, 1H), 3.84 - 3.79 (m, 3H), 3.78 - 3.73 (m, 4H), 3.55 (dd,J=11.7, 1.7 Hz, 1H).

[0714] Example 83 Preparation of (2S,3R,4S,5S)-2-(4-(5-methoxy-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0715]

[0716] Example 83 was able to obtain the target compound using the same method as Example 82.

[0717] 1 H NMR (400 MHz, CD3OD) δ 7.49 (d,J= 8.8 Hz, 2H), 7.43 (d,J= 3.2 Hz, 1H), 7.41 (d,J= 9.0 Hz, 1H), 7.28 (d,J= 8.8 Hz, 2H), 7.17 (d,J= 2.2 Hz, 1H), 6.87 (dd,J= 9.0, 2.3 Hz, 1H), 6.61 (d,J= 2.8 Hz, 1H), 4.95 (d,J= 7.1 Hz, 1H), 3.96 (dd,J= 12.3, 2.5 Hz, 1H), 3.90 (s, 1H), 3.86 (s, 3H), 3.84 - 3.81 (m, 1H), 3.79 - 3.73 (m, 2H), 3.66 (dd,J= 9.0, 3.4 Hz, 1H).

[0718] Example 84 Preparation of (2R,3R,4S,5S)-2-((4'-methoxy-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol

[0719]

[0720] Example 84 was able to obtain the target compound using the same method as Example 80.

[0721] 1 H NMR (400 MHz, DMSO-d6) δ 7.51 (dd,J= 8.8, 2.9 Hz, 4H), 7.08 (d,J= 8.7 Hz, 2H), 6.97 (d,J= 8.8 Hz, 2H), 5.45 (d,J= 2.2 Hz, 1H), 3.80 (d,J= 9.4 Hz, 3H), 3.74 (s, 3H), 3.69 (d,J= 11.8 Hz, 1H), 3.50 (d,J= 10.4 Hz, 1H).

[0722] Example 85 Preparation of (2R,3R,4S,5S)-2-(4-(6-methoxypyridin-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0723]

[0724] Example 85 was able to obtain the target compound using the same method as Example 80.

[0725] 1 H NMR (400 MHz, DMSO-d6) δ 8.38 (d,J= 1.9 Hz, 1H), 7.94 (dd,J= 8.6, 2.5 Hz, 1H), 7.56 (d,J= 8.7 Hz, 2H), 7.11 (d,J= 8.7 Hz, 2H), 6.87 (d,J= 8.7 Hz, 1H), 5.47 (s, 1H), 3.79 (s, 3H), 3.72 (s, 3H), 3.69 (d,J= 12.2 Hz, 1H), 3.50 (dd,J= 11.9, 1.8 Hz, 1H).

[0726] Example 86 Preparation of (2R,3R,4S,5S)-2-((4'-isopropyl-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol

[0727]

[0728] Example 86 was able to obtain the target compound using the same method as Example 80.

[0729] 1 H NMR (400 MHz, CD3OD) δ 7.62 (d,J= 8.7 Hz, 2H), 7.58 (d,J= 8.2 Hz, 2H), 7.35 (d,J= 8.1 Hz, 2H), 7.22 (d,J= 8.7 Hz, 2H), 5.60 (d,J= 2.9 Hz, 1H), 3.97 (dd,J= 7.3, 4.1 Hz, 3H), 3.92 (d,J= 12.8 Hz, 1H), 3.68 (d,J= 10.9 Hz, 1H), 3.02 - 2.94 (m, 1H), 1.32 (d,J= 6.9 Hz, 6H).

[0730] Example 87 Preparation of (2S,3R,4S,5S)-2-((4'-isopropyl-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol

[0731]

[0732] Example 87 was able to obtain the target compound using the same method as Example 80.

[0733] 1 H NMR (400 MHz, CD3OD) δ 7.60 (d,J= 8.8 Hz, 2H), 7.56 (d,J= 8.2 Hz, 2H), 7.34 (d,J= 8.1 Hz, 2H), 7.17 (d,J= 8.7 Hz, 2H), 4.93 (d,J= 7.1 Hz, 1H), 3.93 (d,J= 12.3 Hz, 1H), 3.88 (s, 1H), 3.83 - 3.78 (m, 1H), 3.74 (d,J= 11.4 Hz, 1H), 3.64 (dd,J= 9.0, 3.4 Hz, 1H), 2.97 (dt,J= 14.1, 7.1 Hz, 1H), 1.31 (d,J= 6.9 Hz, 6H).

[0734] Example 88 Preparation of (2R,3R,4S,5S)-2-(4-(6-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0735]

[0736] Example 88 was able to obtain the target compound using the same method as Example 1.

[0737] 1H NMR (400 MHz, CD3OD) δ 8.21 (d,J= 8.9 Hz, 2H), 7.67 (d,J= 8.1 Hz, 1H), 7.61 (s, 1H), 7.35 (d,J= 8.9 Hz, 3H), 5.71 (d,J= 1.0 Hz, 1H), 4.00 (s, 2H), 3.96 (s, 1H), 3.88 (d,J= 11.5 Hz, 1H), 3.70 (dd,J= 12.4, 2.2 Hz, 1H), 3.12 (dt,J= 13.7, 7.0 Hz, 1H), 1.36 (d,J= 6.9 Hz, 6H).

[0738] Example 89 Preparation of (2S,3R,4S,5S)-2-(4-(6-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0739]

[0740] Example 89 was able to obtain the target compound using the same method as Example 1.

[0741] 1 H NMR (400 MHz, CD3OD) δ 8.15 (d,J= 8.9 Hz, 2H), 7.59 (d,J= 8.2 Hz, 1H), 7.53 (s, 1H), 7.29 (d,J= 8.2 Hz, 1H), 7.25 (d,J= 8.9 Hz, 2H), 5.00 (d,J= 7.1 Hz, 1H), 3.96 (dd,J= 12.3, 2.6 Hz, 1H), 3.90 (s, 1H), 3.89 - 3.83 (m, 1H), 3.78 (d,J= 11.3 Hz, 1H), 3.66 (dd,J= 9.0, 3.4 Hz, 1H), 3.07 (dt,J= 13.8, 7.1 Hz, 1H), 1.32 (d,J= 6.9 Hz, 6H).

[0742] Example 90 Preparation of (2R,3R,4S,5S)-2-(4-(5-methyl-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0743]

[0744] Example 90 was able to obtain the target compound using the same method as Example 82.

[0745] 1 H NMR (400 MHz, DMSO-d6) δ 7.50 (d,J= 3.1 Hz, 1H), 7.46 (d,J= 8.9 Hz, 2H), 7.40 (s, 1H), 7.35 (d,J= 8.4 Hz, 1H), 7.20 (d,J= 8.9 Hz, 2H), 6.98 (d,J= 8.3 Hz, 1H), 6.54 (d,J= 3.1 Hz, 1H), 5.49 (s, 1H), 4.98 (d,J= 5.1 Hz, 1H), 4.77 (d,J= 4.4 Hz, 1H), 4.69 (d,J= 3.5 Hz, 1H), 3.79 (s, 3H), 3.72 (d,J= 11.7 Hz, 1H), 3.53 (d,J= 9.8 Hz, 1H), 2.37 (s, 3H).

[0746] Example 91 Preparation of (2R,3R,4S,5S)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0747]

[0748] Example 91 was able to obtain the target compound using the same method as Example 1.

[0749] 1 H NMR (400 MHz, CD3OD) δ 8.20 (d,J= 8.9 Hz, 2H), 7.60 (d,J= 8.8 Hz, 1H), 7.34 (d,J= 8.9 Hz, 2H), 7.29 (d,J= 2.3 Hz, 1H), 7.03 (dd,J= 8.9, 2.5 Hz, 1H), 5.70 (s, 1H), 4.00 (s, 2H), 3.96 (s, 1H), 3.88 (d,J= 15.2 Hz, 4H), 3.70 (dd,J= 12.3, 2.2 Hz, 1H).

[0750] Example 92 Preparation of (2S,3R,4S,5S)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0751]

[0752] Example 92 was able to obtain the target compound using the same method as Example 1.

[0753] 1 H NMR (400 MHz, CD3OD) δ 8.19 (d,J= 8.9 Hz, 2H), 7.60 (d,J= 8.9 Hz, 1H), 7.29 (d,J= 8.8 Hz, 3H), 7.02 (dd,J= 8.9, 2.5 Hz, 1H), 5.04 (d,J= 7.1 Hz, 1H), 3.95 (dd,J= 12.3, 2.6 Hz, 1H), 3.90 (s, 4H), 3.84 (dd,J= 8.8, 7.3 Hz, 1H), 3.80 (d,J= 12.2 Hz, 1H), 3.66 (dd,J= 9.0, 3.4 Hz, 1H).

[0754] Example 93 Preparation of (2R,3R,4S,5R)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0755]

[0756] Example 93 was able to obtain the target compound using the same method as Example 1.

[0757] 1H NMR (400 MHz, CD3OD) δ 8.21 (d,J= 8.8 Hz, 2H), 7.60 (d,J= 9.0 Hz, 1H), 7.34 (d,J= 8.9 Hz, 2H), 7.28 (d,J= 2.3 Hz, 1H), 7.03 (dd,J= 8.9, 2.5 Hz, 1H), 5.66 (d,J= 3.4 Hz, 1H), 3.91 (s, 3H), 3.83 - 3.78 (m, 1H), 3.68 (dd,J= 9.8, 4.8 Hz, 1H), 3.63 - 3.56 (m, 2H), 3.53 (d,J= 10.0 Hz, 1H).

[0758] Example 94 Preparation of (2S,3R,4S,5R)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0759]

[0760] Example 94 was able to obtain the target compound using the same method as Example 1.

[0761] 1 H NMR (400 MHz, CD3OD) δ 8.19 (d,J= 8.9 Hz, 2H), 7.59 (d,J= 8.8 Hz, 1H), 7.27 (dd,J= 5.6, 3.1 Hz, 3H), 7.02 (dd,J= 8.9, 2.5 Hz, 1H), 5.06 (d,J= 7.0 Hz, 1H), 3.96 (dd,J= 11.2, 5.1 Hz, 1H), 3.90 (s, 3H), 3.59 (dd,J= 15.9, 7.3 Hz, 1H), 3.51 - 3.42 (m, 3H).

[0762] Example 95 Preparation of (2R,3R,4S,5S)-2-(4-(6-ethylbenzofuran-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0763]

[0764] Example 95 was able to obtain the target compound using the same method as Example 1.

[0765] 1 H NMR (400 MHz, CD3OD) δ 7.98 (s, 1H), 7.78 (d,J= 8.0 Hz, 1H), 7.67 (d,J= 8.7 Hz, 2H), 7.42 (s, 1H), 7.26 (d,J= 8.8 Hz, 2H), 7.22 (d,J= 8.6 Hz, 1H), 5.61 (d,J= 3.0 Hz, 1H), 4.01 - 3.92 (m, 4H), 3.69 (d,J= 10.4 Hz, 1H), 2.81 (q,J= 7.6 Hz, 2H), 1.32 (t,J= 7.6 Hz, 3H).

[0766] Example 96 Preparation of (2S,3R,4S,5S)-2-(4-(6-ethylbenzofuran-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0767]

[0768] Example 96 was able to obtain the target compound using the same method as Example 1.

[0769] 1 H NMR (400 MHz, CD3OD) δ 8.01 (s, 1H), 7.79 (d,J= 8.1 Hz, 1H), 7.68 (d,J= 8.7 Hz, 2H), 7.44 (s, 1H), 7.23 (dd,J= 7.7, 4.4 Hz, 3H), 4.95 (d,J= 7.1 Hz, 1H), 3.95 (dd,J= 12.3, 2.5 Hz, 1H), 3.89 (s, 1H), 3.85 - 3.80 (m, 1H), 3.75 (d,J= 11.5 Hz, 1H), 3.65 (dd,J= 9.1, 3.4 Hz, 1H), 2.81 (q,J= 7.6 Hz, 2H), 1.32 (t,J= 7.6 Hz, 3H).

[0770] Example 97 Preparation of (2R,3R,4S,5S)-2-(3-(7-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0771]

[0772] Example 97 was able to obtain the target compound using the same method as Example 1.

[0773] 1 H NMR (400 MHz, CD3OD) δ 8.02 (s, 1H), 7.94 (d,J= 7.7 Hz, 1H), 7.62 (dd,J= 7.8, 0.9 Hz, 1H), 7.58 (t,J= 8.0 Hz, 1H), 7.38 (ddd,J= 26.3, 11.3, 4.8 Hz, 3H), 5.69 (d,J= 2.7 Hz, 1H), 4.02 (t,J= 3.3 Hz, 2H), 3.99 - 3.93 (m, 2H), 3.73 (dd,J= 12.2, 1.9 Hz, 1H), 3.48 (dt,J=13.7, 7.0 Hz, 1H), 1.49 (d,J= 6.9 Hz, 6H).

[0774] Example 98 Preparation of (2S,3R,4S,5S)-2-(3-(7-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0775]

[0776] Example 98 was able to obtain the target compound using the same method as Example 1.

[0777] 1H NMR (400 MHz, CD3OD) δ 7.96 (s, 1H), 7.94 (d,J= 7.9 Hz, 1H), 7.61 (dd,J= 7.8, 0.9 Hz, 1H), 7.57 (t,J= 7.9 Hz, 1H), 7.35 (ddd,J= 13.7, 11.8, 7.5 Hz, 3H), 5.01 (d,J= 7.1 Hz, 1H), 4.01 - 3.97 (m, 1H), 3.92 (s, 1H), 3.89 - 3.85 (m, 1H), 3.81 (d,J= 11.8 Hz, 1H), 3.68 (dd,J=9.1, 3.3 Hz, 1H), 3.47 (dt,J= 13.9, 6.9 Hz, 1H), 1.49 (d,J= 7.0 Hz, 6H).

[0778] Example 99 Preparation of (2R,3R,4S,5S)-2-(2-chloro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0779]

[0780] Example 99 was able to obtain the target compound using the same method as Example 1.

[0781] 1 H NMR (400 MHz, CD3OD) δ 8.31 - 8.26 (m, 1H), 8.18 (dd,J= 8.2, 1.3 Hz, 1H), 7.64 - 7.59 (m, 2H), 7.55 (d,J= 8.7 Hz, 1H), 7.30 (d,J= 8.0 Hz, 1H), 5.90 (d,J= 1.4 Hz, 1H), 4.08 (s, 2H), 3.99 (s, 1H), 3.90 (d,J= 12.7 Hz, 1H), 3.71 (d,J= 12.5 Hz, 1H), 2.53 (s, 3H).

[0782] Example 100 Preparation of (2S,3R,4S,5S)-2-(2-chloro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0783]

[0784] Example 100 was able to obtain the target compound using the same method as Example 1.

[0785] 1 H NMR (400 MHz, CD3OD) δ 8.28 (d,J= 2.0 Hz, 1H), 8.19 (dd,J= 8.7, 2.0 Hz, 1H), 7.67 (d,J= 8.4 Hz, 1H), 7.63 (s, 1H), 7.52 (d,J= 8.8 Hz, 1H), 7.31 (d,J= 8.4 Hz, 1H), 5.21 (d,J= 6.9 Hz, 1H), 3.93 (dd,J= 12.1, 3.1 Hz, 1H), 3.90 - 3.85 (m, 2H), 3.79 (d,J= 11.4 Hz, 1H), 3.66 (dd,J= 8.6, 3.3 Hz, 1H), 2.54 (s, 3H).

[0786] Example 101 Preparation of (2R,3R,4S,5R)-2-(2-fluoro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0787]

[0788] Example 101 was able to obtain the target compound using the same method as Example 1.

[0789] 1 H NMR (400 MHz, DMSO-d6) δ7.23 (dt,J= 9.2, 5.0 Hz, 3H), 6.97 - 6.90 (m, 3H), 6.73 (ddd,J= 9.0, 2.9, 1.5 Hz, 1H), 5.37 (d,J= 3.6 Hz, 1H), 5.14 (d,J= 5.8 Hz, 1H), 5.04 (s, 1H), 5.01 (d,J= 4.9 Hz, 1H), 3.58 - 3.34 (m, 5H), 2.86 (p,J= 6.9 Hz, 1H), 1.17 (d,J= 6.9 Hz, 6H).

[0790] Example 102 Preparation of (2S,3R,4S,5S)-2-(2-chloro-4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0791]

[0792] Example 102 was able to obtain the target compound using the same method as Example 1.

[0793] 1 H NMR (400 MHz, CD3OD) δ 8.26 (d,J= 2.0 Hz, 1H), 8.16 (dd,J= 8.7, 2.0 Hz, 1H), 7.64 (d,J= 8.9 Hz, 1H), 7.49 (d,J= 8.8 Hz, 1H), 7.32 (d,J= 2.3 Hz, 1H), 7.06 (dd,J= 8.9, 2.5 Hz, 1H), 5.19 (d,J= 6.8 Hz, 1H), 4.00 - 3.88 (m, 6H), 3.81 (d,J= 11.8 Hz, 1H), 3.69 (dd,J= 8.7, 3.3 Hz, 1H).

[0794] Example 103 Preparation of (2R,3R,4S,5S)-2-(2-chloro-4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0795]

[0796] Example 103 was able to obtain the target compound using the same method as Example 1.

[0797] 1H NMR (400 MHz, CD3OD) δ8.24 (d,J= 2.0 Hz, 1H), 8.14 (dd,J= 8.7, 2.1 Hz, 1H), 7.60 (d,J= 8.9 Hz, 1H), 7.51 (d,J= 8.8 Hz, 1H), 7.28 (d,J= 2.4 Hz, 1H), 7.03 (dd,J= 8.9, 2.5 Hz, 1H), 5.87 (d,J= 2.8 Hz, 1H), 4.12 - 4.04 (m, 2H), 3.99 (s, 1H), 3.91 (d,J= 9.7 Hz, 4H), 3.71 (dd,J= 12.3, 1.9 Hz, 1H).

[0798] Example 104 Preparation of (2S,3R,4S,5S)-2-(2-fluoro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0799]

[0800] Example 104 was able to obtain the target compound using the same method as Example 1.

[0801] 1 H NMR (400 MHz, CD3OD) δ 8.04 (t,J= 9.2 Hz, 2H), 7.66 - 7.56 (m, 2H), 7.51 (t,J= 8.6 Hz, 1H), 7.30 (d,J= 8.4 Hz, 1H), 5.14 (d,J= 7.0 Hz, 1H), 3.97 (dd,J= 12.2, 2.7 Hz, 1H), 3.93 - 3.86 (m, 2H), 3.80 (d,J= 12.1 Hz, 1H), 3.68 (dd,J= 8.8, 3.4 Hz, 1H), 2.53 (s, 3H).

[0802] Example 105 Preparation of (2R,3R,4S,5S)-2-(2-fluoro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0803]

[0804] Example 105 was able to obtain the target compound using the same method as Example 1.

[0805] 1 H NMR (400 MHz, CD3OD) δ 8.03 (dd,J= 15.6, 5.1 Hz, 2H), 7.66 - 7.50 (m, 3H), 7.30 (d,J= 8.2 Hz, 1H), 5.79 (d,J= 1.7 Hz, 1H), 4.08 - 3.90 (m, 4H), 3.73 (dd,J= 12.3, 2.0 Hz, 1H), 2.53 (s, 3H).

[0806] Example 106 Preparation of (2S,3R,4S,5S)-2-(3-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0807]

[0808] Example 106 was able to obtain the target compound using the same method as Example 1.

[0809] 1 H NMR (400 MHz, CD3OD) δ 7.96 (d,J= 7.9 Hz, 2H), 7.73 (d,J= 8.8 Hz, 1H), 7.63 (t,J= 8.1 Hz, 1H), 7.43 - 7.36 (m, 2H), 7.13 (dd,J= 8.8, 2.6 Hz, 1H), 5.07 (d,J= 7.0 Hz, 1H), 3.98 (d,J= 15.5 Hz, 4H), 3.91 (s, 1H), 3.84 (dd,J= 16.1, 9.7 Hz, 2H), 3.69 (dd,J= 8.8, 3.4 Hz, 1H).

[0810] Example 107 Preparation of (2R,3R,4S,5S)-2-(3-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0811]

[0812] Example 107 was able to obtain the target compound using the same method as Example 1.

[0813] 1 H NMR (400 MHz, CD3OD) δ 8.01 (s, 1H), 7.96 (d,J= 7.8 Hz, 1H), 7.74 (d,J= 8.9 Hz, 1H), 7.63 (t,J= 8.0 Hz, 1H), 7.43 (d,J= 2.5 Hz, 2H), 7.13 (dd,J= 8.9, 2.5 Hz, 1H), 5.72 (d,J= 2.0 Hz, 1H), 4.02 (s, 2H), 3.99 - 3.91 (m, 5H), 3.74 (dd,J= 12.2, 2.0 Hz, 1H).

[0814] Example 108 Preparation of (2S,3R,4S,5S)-2-(4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0815]

[0816] Example 108 was able to obtain the target compound using the same method as Example 1.

[0817] 1 H NMR (400 MHz, CD3OD) δ 8.25 (d,J= 8.9 Hz, 2H), 7.65 (d,J= 8.4 Hz, 1H), 7.62 (s, 1H), 7.35 - 7.28 (m, 3H), 5.08 (d,J= 7.1 Hz, 1H), 3.96 (dd,J= 12.2, 2.7 Hz, 1H), 3.90 (s, 1H), 3.82 (dd,J= 14.3, 8.3 Hz, 2H), 3.66 (dd,J= 8.9, 3.5 Hz, 1H), 2.55 (s, 3H).

[0818] Example 109 Preparation of (2R,3R,4S,5S)-2-(4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0819]

[0820] Example 109 was able to obtain the target compound using the same method as Example 1.

[0821] 1 H NMR (400 MHz, CD3OD) δ 8.21 (d,J= 8.9 Hz, 2H), 7.59 (d,J= 8.3 Hz, 1H), 7.56 (s, 1H), 7.34 (d,J= 8.9 Hz, 2H), 7.26 (d,J= 8.2 Hz, 1H), 5.71 (s, 1H), 4.01 (s, 2H), 3.96 (s, 1H), 3.89 (d,J= 12.3 Hz, 1H), 3.70 (dd,J= 12.3, 2.1 Hz, 1H).

[0822] Example 110 Preparation of (2R,3R,4S,5S)-2-(4-phenethylphenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0823]

[0824] Example 110 was able to obtain the target compound using the same method as Example 1.

[0825] 1 H NMR (400 MHz, DMSO-d6) δ 7.27 - 7.08 (m, 7H), 6.93 - 6.88 (m, 2H), 5.35 (d,J= 2.5 Hz, 1H), 4.95 (d,J= 5.7 Hz, 1H), 4.75 (d,J= 4.7 Hz, 1H), 4.68 (d,J= 3.5 Hz, 1H), 3.77 - 3.70 (m, 3H), 3.66 (d,J= 11.9 Hz, 1H), 3.47 - 3.44 (m, 1H), 2.87 - 2.73 (m, 4H).

[0826] MS(m / z): 331.2 [M+H] +

[0827] Example 111 Preparation of (2R,3R,4S,5S)-2-(4-((E)-styryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0828]

[0829] Example 111 was able to obtain the target compound using the same method as Example 1.

[0830] 1 H NMR (400 MHz, DMSO-d6) δ7.54 (dd,J= 10.4, 8.2 Hz, 4H), 7.34 (t,J= 7.6 Hz, 2H), 7.25 - 7.20 (m, 1H), 7.17 (s, 1H), 7.11 (s, 1H), 7.03 (d,J= 8.7 Hz, 2H), 5.46 (s, 1H), 4.96 (d,J= 5.4 Hz, 1H), 4.76 (d,J= 4.9 Hz, 1H), 4.68 (d,J= 3.6 Hz, 1H), 3.80 - 3.73 (m, 3H), 3.67 (d,J= 11.7 Hz, 1H), 3.50 (dd,J= 12.0, 2.2 Hz, 1H.

[0831] MS(m / z): 351.1 [M+ Na] +

[0832] Example 112 Preparation of (2R,3R,4S,5S)-2-(4-(bis(4-methoxyphenyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0833]

[0834] Example 112 was able to obtain the target compound using the same method as Example 1.

[0835] MS(m / z): 329.2 [M+H] +

[0836] Example 113 Preparation of (2R,3R,4S,5S)-2-((4'-(4-isopropylbenzyl)-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol

[0837]

[0838] Example 113 was able to obtain the target compound using the same method as Example 1.

[0839] 1 H NMR (400 MHz, DMSO-d6) δ 7.56 - 7.48 (m, 4H), 7.28 - 7.23 (m, 2H), 7.14 (d,J= 1.1 Hz, 4H), 7.10 - 7.05 (m, 2H), 5.46 (d,J= 2.4 Hz, 1H), 4.96 (d,J= 5.4 Hz, 1H), 4.76 (d,J= 4.8 Hz, 1H), 4.67 (d,J= 3.6 Hz, 1H), 3.89 (s, 2H), 3.81 - 3.74 (m, 3H), 3.68 (d,J= 11.8 Hz, 1H), 3.49 (dd,J= 12.0, 2.4 Hz, 1H), 2.81 (p,J= 6.9 Hz, 1H), 1.15 (d,J= 6.9 Hz, 6H).

[0840] MS(m / z): 435.5 [M+H] +

[0841] Example 114 Preparation of furan-2-yl(4-(((2S,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone

[0842]

[0843] Example 114 was synthesized through Manufacturing Example 2, and the target compound was obtained by hydrolysis according to Manufacturing Example 5 after introduction of a substituent in the α / β form.

[0844] 1H NMR (400 MHz, DMSO-d6) δ 8.10 (d,J= 0.8 Hz, 1H), 7.94 (d,J= 8.9 Hz, 2H), 7.40 - 7.37 (m, 1H), 7.16 (d,J= 8.8 Hz, 2H), 6.78 (dd,J= 3.5, 1.7 Hz, 1H), 5.30 (d,J= 5.1 Hz, 1H), 5.01 (d,J= 6.8 Hz, 1H), 4.90 (d,J= 5.6 Hz, 1H), 4.70 (d,J= 4.1 Hz, 1H), 3.75 - 3.63 (m, 4H), 3.51 - 3.47 (m, 1H).

[0845] Example 115 Preparation of furan-2-yl(4-(((2R,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone

[0846]

[0847] Example 115 was able to obtain the target compound using the same method as Example 114.

[0848] 1 H NMR (400 MHz, DMSO-d6) δ 8.10 (d,J= 0.9 Hz, 1H), 7.94 (d,J= 8.7 Hz, 2H), 7.40 - 7.37 (m, 1H), 7.19 (d,J= 8.8 Hz, 2H), 6.78 (dd,J= 3.5, 1.5 Hz, 1H), 5.61 (d,J= 0.9 Hz, 1H), 5.07 - 5.04 (m, 1H), 4.83 (d,J= 3.4 Hz, 1H), 4.74 (d,J= 3.4 Hz, 1H), 3.80 (d,J= 8.4 Hz, 3H), 3.67 (d,J= 11.8 Hz, 1H), 3.54 (dd,J= 11.9, 2.0 Hz, 1H).

[0849] Example 116 Preparation of (2R,3R,4S,5S)-2-(4-(4-methoxyphenethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0850]

[0851] Example 116 was synthesized through step 15 of Manufacturing Example 1, and the target compound was obtained by hydrolysis according to Manufacturing Example 5 after introduction of a substituent in the α / β form.

[0852] 1 H NMR (400 MHz, DMSO-d6) δ7.09 (d,J= 8.6 Hz, 4H), 6.94 - 6.87 (m, 2H), 6.85 - 6.76 (m, 2H), 5.36 (d,J= 2.4 Hz, 1H), 4.91 (d,J= 5.7 Hz, 1H), 4.74 (d,J= 4.8 Hz, 1H), 4.65 (d,J= 3.5 Hz, 1H), 3.79 - 3.71 (m, 3H), 3.67 (d,J= 13.6 Hz, 4H), 3.47 (dd,J= 12.0, 2.3 Hz, 1H), 2.75 (s, 4H).

[0853] MS(m / z): 361.4 [M+H] +

[0854] Example 117 Preparation of (2R,3R,4S,5S)-2-(4-(4-isopropylphenethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0855]

[0856] Example 117 was able to obtain the target compound using the same method as Example 116.

[0857] MS(m / z): 373.4 [M+H] +

[0858] Example 118 Preparation of (2R,3R,4S,5S)-2-(4-((E)-4-methoxystyryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0859]

[0860] Example 118 was able to obtain the target compound using the same method as Example 116.

[0861] MS(m / z): 359.3 [M+H] +

[0862] Example 119 Preparation of (2R,3R,4S,5S)-2-(4-((E)-4-isopropylstyryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0863]

[0864] Example 119 was able to obtain the target compound using the same method as Example 116.

[0865] MS(m / z): 371.4 [M+H] +

[0866] Example 120 Preparation of (2R,3R,4S,5S)-2-(4-(benzo[d][1,3]dioxol-5-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0867]

[0868] Example 120 was able to obtain the target compound using the same method as Example 1.

[0869] MS(m / z): 347.3 [M+H] +

[0870] Example 121 Preparation of (2R,3R,4S,5S)-2-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0871]

[0872] Example 121 was able to obtain the target compound using the same method as Example 1.

[0873] MS(m / z): 361.3 [M+H] +

[0874] Example 122 Preparation of (2R,3R,4S,5S)-2-((4'-chloro-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol

[0875]

[0876] Example 122 was able to obtain the target compound using the same method as Example 1.

[0877] 1 H NMR (400 MHz, DMSO-d6) δ 7.66 - 7.54 (m, 4H), 7.50 - 7.37 (m, 2H), 7.14 - 7.07 (m, 2H), 5.48 (d,J= 2.3 Hz, 1H), 4.98 (d,J= 4.5 Hz, 1H), 4.78 (s, 1H), 4.69 (d,J= 3.5 Hz, 1H), 3.77 (s, 3H), 3.68 (d,J= 11.8 Hz, 1H), 3.50 (dd,J= 11.9, 2.5 Hz, 1H).

[0878] MS(m / z): 337.7 [M+H] +

[0879] Example 123 Preparation of (2R,3R,4S,5S)-2-((4''-isopropyl-[1,1':4',1''-terphenyl-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol

[0880]

[0881] Example 123 was able to obtain the target compound using the same method as Example 1.

[0882] MS(m / z): 421.5 [M+H] +

[0883] Example 124 Preparation of (2R,3R,4S,5S)-2-(3-(phenylethynyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol

[0884]

[0885] Example 124 was synthesized through step 14 of Manufacturing Example 1, and the target compound was obtained by hydrolysis according to Manufacturing Example 5 after introduction of a substituent in the α / β form.

[0886] MS(m / z): 327.3 [M+H] +

[0887] Example A: Purification

[0888] A mixture of 1 kg of the active ingredient of the compound according to an embodiment of the present invention, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate was compressed in a conventional manner to obtain tablets, each tablet containing 10 mg of the active ingredient.

[0889] Example B: Aqueous solution or suspension

[0890] 1 g of the active ingredient of the compound according to the present invention, NaH2PO in 940 ml of twice-distilled water 4 ° 2H2O 9.38g, Na2HPO 4 ° Prepare a solution from 28.48 g of 12H2O and 0.1 g of benzalkonium chloride. Adjust the pH to 6.8, make 1 L of the solution, and sterilize by irradiation. This solution can be used as an eye drop.

[0891] Example C: Injectable solution

[0892] A solution of 100 g of the active ingredient of the compound according to the present invention and 5 g of sodium hydrogen phosphate in 3 L of double-distilled water is adjusted to pH 6.5 using 2N hydrochloric acid, sterile filtered, transferred to injection vials, lyophilized under sterile conditions, and sealed under sterile conditions. Each injection vial contains 5 mg of the active ingredient.

[0893] Experimental Example 1. In vitro drug efficacy evaluation: HRE (hypoxia response element) luciferase assay

[0894] In the case of AD patients, the brain is mostly not supplied with blood smoothly, so the oxygen concentration is up to 50% lower than that of a normal person, and it has been reported that various oxidative stresses (ROS) and neuroinflammation increase as a result. It has been studied that when the HIF-1α (hypoxia inducible factor-1) factor combines with HRE (hypoxia response element), it increases VEGF (vascular endothelial growth factor), which promotes the formation of new blood vessels, and this increases the oxygen concentration in the brain and helps suppress damage to nerve cells.

[0895] A reporter gene using luciferase, which can confirm the level of HRE expression, was inserted into HEK-293 cells, which are human embryonic kidney cells, and a plasmid (HRE / Luc) with luciferase attached downstream of the promoter of HRE that binds to HIF-1α was inserted using lipofectamine (Invitrogen) to construct HRE / Luc / HEK293 cells.

[0896] To perform the HRE luciferase assay, HRE / Luc / HEK293 cells were seeded at 4X10 in Minimum Essential Medium (MEM) containing 10% fetal bovine serum. 4Cells were seeded into 96-well culture plates at a density of 10 cells / well, and after 1 day, the medium of the cells was discarded and replaced with a medium containing the compounds of the examples at different concentrations. Six hours after compound pretreatment, HRE / Luc / HEK293 cells were cultured for 18 hours under hypoxic (O20.1%) culture conditions, and then washed with phosphate buffer, lysed with lysis buffer, and luciferase reagent (Promega) for luciferase assay was added. Afterwards, the amount of luminescence was measured using Infinite200 (Tecan), and the change in HRE expression level was evaluated in relation to HIF-1 signaling.

[0897] Changes in HRE expression levels for the compounds of the present invention (HRE luciferase assay results) are as described in Table 2 below. As a result of evaluating 35 compounds among Examples 1 to 36, a number of compounds were identified that induced an increase in HRE activity of more than two times at the same treatment concentration (100 uM). In particular, compounds of Examples 7, 8, 27, 33, 35, and 36 were identified to induce HRE expression at a level more than three times higher at a low concentration of 10 uM. (Table 2). In addition, as a result of evaluating 69 compounds among Examples 37 to 109, a number of compounds were identified that induced an increase in HRE activity of more than three times at the same treatment concentration (10 μM). In particular, compounds of Examples 41, 43, 57, 67, 68, 92, 94, 102, 104, 106, 107, 108, and 109 were identified to induce HRE expression at a level more than three times higher even at a low concentration of 1 μM. (Table 2)

[0898]

[0899] Experimental Example 2. In vivo efficacy evaluation: Scopolamine-induced cognitive impairment model

[0900] The cognitive function-improving effects of some of the compounds that showed excellent efficacy in the previously described in vitro assay were evaluated in an animal model.

[0901] A rodent animal model of memory impairment induced by intraperitoneal administration of scopolamine was used, and the memory was evaluated using the Y-maze test and the Passive Avoidance Test (PAT). Scopolamine is a muscarinic acetylcholine receptor antagonist and is a representative experimental model that shows cognitive dysfunction similar to AD patients due to blockade of neurotransmitters when administered to animals. The Y-maze test and passive avoidance test, which are general and representative methods, were used as cognitive function evaluation techniques. In order to objectify the efficacy level of the compounds, a group administered donepezil (Aricept, Eisa) was separately set aside as a positive control to compare the efficacy level of the compounds.

[0902] For the cognitive function evaluation, 5-week-old male ICR mice were used, and the compounds to be evaluated were prepared at a dosage of 50 mg / kg / ml and administered orally repeatedly at a fixed time for 7 days, and the positive control substance was administered at 5 mg / kg / ml. After the final administration, 1 mg / kg / 2 ml of scopolamine was administered intraperitoneally, and 30 minutes later, the Y-maze test and passive avoidance test, which are cognitive function evaluations, were performed.

[0903] The Y-maze test is a test to measure short-term memory and is a method to evaluate the ability to act sequentially. The measuring device consists of three branches, each 42 cm long, 3 cm wide, and 12 cm high, and the angle at which the three branches fold is 120°. The experimental animal was placed in each branch for 8 minutes, and the number of times the animal's tail entered each branch and the cases in which the animal entered each branch in sequence (actual alternation) were scored. Alternation behavior was defined as entering all three branches without overlapping, and was calculated using the following mathematical formula.

[0904] [Mathematical formula]

[0905] Spontaneous alteration (%) = Actual alternation / Maximum alternation x 100 (Maximum alternation: Total number of entries - 2)

[0906] In addition, the passive avoidance experiment was conducted using an avoidance learning box (Jeongdo B&P Co., Ltd., Seoul, Republic of Korea). The avoidance learning box is divided into a dark room and a bright room. When the experimental animal is placed in the bright room, it moves to the dark room. At that moment, an electric shock of 0.5 mA is applied for 5 seconds, and when the experimental animal is placed back in the bright room the next day, it remembers the electric shock in the dark room and stays in the bright room. The time it stays in this room (step-through latency) is measured to evaluate memory. The efficacy of the compounds of the present invention compared to the normal group and the control group in the Y-maze test and passive avoidance test is described in Table 3 (Scopolamine-induced cognitive impairment model results) below.

[0907] The experimental results are shown in Table 3 below. The spontaneous change (%) in the Y-maze test and the time (sec) spent in the bright room in the passive avoidance test were investigated, and these were expressed as the efficacy (effect, %) compared to the normal group and control group at that time. As a result, Example 3 showed a cognitive function recovery of 59% and 91% compared to normal animals in the Y-maze test and passive avoidance test, which were equal to or higher than the positive control substance donepezil (same set 35%, 94%). In addition, compounds such as Examples 2, 7, 15, 20, 22, 25, 31, 41, and 56 showed an efficacy of 50% or more in the passive avoidance test, and Examples 7, 30, 31, and 56 showed an efficacy of 50% or more in the passive avoidance test.

[0908]

[0909] Experimental Example 3. Ex-vivo Efficacy Evaluation: Long-Term Potentiation (LTP) Experiment

[0910] Long-term potentiation (LTP) experiments are a useful experimental model for assessing synaptic function in memory learning, and their results are particularly valuable in studying memory-related neurodegenerative diseases such as AD. In this experiment, cholinergic neurons, a key component of learning and memory, were temporarily blocked with scopolamine, and then some exemplary compounds were evaluated.

[0911] The hippocampus was extracted from the brain of a 7-day-old rat, and the hippocampal slices were cultured for 14 days using the organotypic hippocampal slice cultures (OHSCs) method before use in the experiment. The cultured brain hippocampal slices were mounted on a microelectrode array (MEA; Multi-Channel Systems, Germany) system and equipped with an MEA1060 amplifier. 300 μM of scopolamine, a neurotoxic stimulant, and 20 μM of the test substance were added to the culture medium. LTP was induced in the CA1 region of the brain, and the response changes were measured as field excitatory postsynaptic potentials (fEPSPs). Long-term potential (LTP) induction was performed using Theta-Burst stimulation (TBS), which consisted of 100 Hz high-frequency stimulation (HFS) for 1 second three times at 5-minute intervals.

[0912] Table 4 shows the results of this Long Term Potentiation (LTP, long-term memory strengthening) experiment. All drug-treated groups showed increased fEPSP values ​​compared to the Scopolamine group, and the degree was in the order of Example 3 194.05% > Example 34 152.49% > Example 36 152.18% > Example 23 139.28% > Example 22 134.14, showing an activity of over 130%. The LTP activity of Example 3 (DM3159) was higher than that of the normal group (147%) and much superior to the activity of donepezil, a global standard AD treatment drug (155.64%).

[0913]

Claims

1. A compound represented by the following chemical formula I, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof: [Chemical Formula I] In the above chemical formula I, R1, R2, and R3 are each hydrogen, hydroxy, methoxy, fluoro, azide, amine, 10-aminodecanoic, acetyl, or benzyl; R4 is hydrogen or methyl; X is oxygen, nitrogen, sulfur or -CH2-; A is phenyl which is unsubstituted or substituted with Y; Substituent Y is hydrogen, straight or branched chain C 1-3 At least one selected from the group consisting of alkyl, and halogen; B is a direct bond, -[CH2] n -, -C(CH3)2-, -C(CF3)2-, -O-, -NH-, -SO2-, , n is an integer from 1 to 3; Ring C is unsubstituted or substituted with Z. 5-7 Cycloalkyl, C 5-7 heterocycloalkyl, phenyl, biphenyl, naphthyl, aryl or heteroaryl; Substituent Z is a straight or branched chain C 1-6 At least one selected from the group consisting of alkyl, cycloalkyl, phenyl, heteroaryl, halogen, amine, cyano, nitro, alkoxy, and thiol.

2. In paragraph 1, At least two of R1, R2, and R3 of the above chemical formula I are each hydroxy; A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen.

3. In paragraph 1, R1, R2, and R3 of the above chemical formula I are each hydroxy; A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen.

4. In paragraph 1, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that X in the chemical formula I is oxygen.

5. In paragraph 1, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that A of the above chemical formula I is unsubstituted phenyl.

6. In paragraph 1, In the above chemical formula I, A is phenyl substituted with Y, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that the substituent Y is a halogen.

7. In paragraph 1, XA of the above chemical formula I is And, Substituent Y is a straight or branched chain C 1-3 A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that it is alkyl or halogen.

8. In paragraph 1, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that B of the above chemical formula I is a direct bond.

9. In paragraph 1, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that B of the above chemical formula I is -CH2-.

10. In paragraph 1, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that B of the above chemical formula I is -O-.

11. In paragraph 1, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that ring C of the above chemical formula I is phenyl which is unsubstituted or substituted with Z.

12. In paragraph 1, The B-ring C of the above chemical formula I is A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that:

13. In paragraph 1, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that ring C of the above chemical formula I is naphthyl, or heteroaryl, which is unsubstituted or substituted with Z.

14. In paragraph 1, Ring C of the above chemical formula I is unsubstituted or substituted with Z. 5-7 Cycloalkyl, C 5-7 A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is a 1-membered, 2-membered, or 3-membered ring compound.

15. In paragraph 1, The B-ring C of the above chemical formula I is A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that:

16. In paragraph 1, The substituent Z of the above chemical formula I is a straight or branched chain C 1-6 A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that it is an alkyl, a halogen, an amine, or an alkoxy.

17. In paragraph 1, The compound of the above chemical formula I is as follows: <1> Inland <124> A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that it is any one selected from the group consisting of: <1> (2R,3R,4S,5S)-2-(4-benzylphenoxy)tetrahydro-2H-pyran-3,4,5-triol, <2> (2R,3R,4S,5S)-2-(4-(4-methylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <3> (2R,3R,4S,5S)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <4> (2S,3R,4S,5S)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-diol, <5> (3S,4S,5R,6R)-5-methoxy-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-diol, <6> (2R,3S,4R,5S,6S)-2-(4-(4-methoxybenzyl)phenoxy)-6-methyltetrahydro-2H-pyran-3,4,5-triol, <7> (2R,3R,4S,5S)-2-(4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <8> (2R,3R,4S,5S)-2-(2-chloro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <9> (2R,3R,4S,5S)-2-(4-(4-phenoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <10> (2R,3R,4S,5S)-2-(4-(4-trifluoromethoxy)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <11> (2R,3R,4S,5S)-2-(4-(4-(methylthio)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <12> (2S,3R,4S,5S)-2-(4-(4-(dimethylamino)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <13> (2R,3R,4S,5S)-2-(4-(4-fluorobenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <14> (2R,3R,4S,5S)-2-(4-(4-chlorobenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <15> (2R,3R,4S,5S)-2-(4-(3-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <16> (2R,3R,4S,5S)-2-(4-(3,5-bis(trifluoromethyl)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <17> (2R,3R,4S,5S)-2-(4-(3,4-dimethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4-triol, <18> (2R,3R,4S,5S)-2-(4-(3,4,5-trimethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <19> (2R,3R,4S,5S)-2-(4-(naphthalen-2-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <20> (2R,3R,4S,5S)-2-(4-(6-methoxynaphthalen-2-yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <21> (2R,3R,4S,5S)-2-(4-(cyclopentylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <22> (2R,3R,4S,5S)-2-(4-(cyclohexylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <23> (2R,3R,4S,5S)-2-(4-(thiophen-3-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <24> (2S,3R,4S,5S)-2-(4-(pyridin-3-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <25> (2R,3R,4S,5S)-2-(3-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <26> (2R,3R,4S,5S)-2-((4-benzylphenyl)thio)tetrahydro-2H-pyran-3,4,5-thiol, <27> (2R,3R,4S,5S)-2-((4-(4-isopropylbenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triol, <28> (2S,3R,4S,5S)-2-((4-(4-isopropylbenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triol, <29> (2R,3R,4S,5S)-2-((4-(4-methoxybenzyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-thiol, <30> (2R,3R,4S,5S)-2-(4-(2-(4-methoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <31> (2R,3R,4S,5S)-2-(4-(2-(4-ethoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <32> (2R,3R,4S,5S)-2-(4-(1,1,1,3,3,3-hexafluoro-2-(4-methoxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <33> (2R,3R,4S,5S)-2-(4-(para-tolyloxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <34> (2R,3R,4S,5S)-2-(4-(3,5-dimethylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <35> (2R,3R,4S,5S)-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <36> (2R,3R,4S,5S)-2-(4-(4-(tert-butyl)phenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <37> (2R,3R,4S,5S)-2-(4-(3-chloro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <38> (2R,3R,4S,5S)-2-(3-chloro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <39> (2R,3R,4S,5S)-2-(4-(4-ethoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <40> (2R,3R,4S,5S)-2-(3-chloro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <41> (2R,3R,4S,5S)-2-(2-fluoro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <42> (2R,3R,4S,5R)-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <43> (2R,3R,4S,5R)-2-(4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <44> (2R,3R,4S,5S)-2-(4-(4-isoproxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <45> (2R,3R,4S,5S)-2-(4-(4-(cyclopentyloxy)benzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <46> (2R,3R,4S,5S)-2-(2-fluoro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <47> (2R,3R,4S,5S)-2-(3-fluoro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <48> (2R,3R,4S,5S)-2-(3-fluoro-4-(4-isopropylbenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <49> (2R,3R,4S,5S)-2-(4-(2-chloro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <50> (2R,3R,4S,5S)-2-(4-(2-fluoro-4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <51> (2R,3R,4S,5S)-2-(2-chloro-4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <52> (2R,3R,4S,5S)-2-(4-((4'-isopropyl-[1,1'-biphenyl]-4-yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <53> (2R,3R,4S,5S)-2-(4-((5-methoxybenzo[d]oxazol-2-yl)methol)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <54> (2R,3R,4S,5S)-2-(3-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <55> (2R,3R,4S,5S)-2-(4-(4-methoxyphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <56> (2R,3R,4S,5R)-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <57> (2R,3R,4S,5S)-2-(2-chloro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <58> (2R,3R,4R,5S)-5-fluoro-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol, <59> (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <60> (2R,3R,4S,5S)-2-(4-(4-isopropylphenoxy)phenoxy)-4-methoxytetrahydro-2H-pyran-3,5-diol <61> (2R,3R,4R,5S)-2-(4-(4-isopropylphenoxy)phenoxy)-5-methoxytetrahydro-2H-pyran-3,4-diol, <62> (3S,4S,5R,6R)-6-(4-(4-isopropylphenoxy)phenoxy)-5-methoxytetrahydro-2H-pyran-3,4-diol, <63> (3S,4S,5R,6R)-5-fluoro-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol, <64> (2R,3R,4R,5R)-5-fluoro-2-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol, <65> (3S,4S,5S,6R)-5-fluoro-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol, <66> (3S,4R,6R)-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol, <67> (2R,3R,4S,5R)-2-(2-chloro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <68> (2R,3R,4S,5S)-2-(2-fluoro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <69> (3S,4R,5R,6R)-5-azido-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol, <70> (3S,4R,5R,6R)-5-amino-6-(4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4-diol, <71> (4-methoxyphenyl)(4-(((2R,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone, <72> 4-(4-(((2S,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)benzoyl)benzonitrile, <73> (2R,3R,4S,5S)-2-(4-(((1r,4R)-4-ethylcyclohexyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <74> (2R,3R,4S,5S)-2-(4-(((1r,4R)-4-isopropylcyclohexyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <75> (2S,3R,4S,5S)-2-(4-(pyrrolidin-1-ylmethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <76> (2S,3R,4S,5S)-2-(4-(morpholinomethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <77> (3S,4R,5R,6R)-5-azido-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran)-3,4-diol, <78> (3S,4R,5R,6R)-5-azido-6-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran)-3,4-diol, <79> (2R,3R,4S,5S)-4,5-dihydroxy-2-(4-(4-methoxybenzyl)phenoxy)tetrahydro-2H-pyran-3-yl 10-aminodecanoate, <80> (2R,3R,4S,5S)-2-((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol, <81> (2R,3R,4S,5S)-2-(4-(6-methoxybenzofuran-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <82> (2R,3R,4S,5S)-2-(4-(5-methoxy-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <83> (2S,3R,4S,5S)-2-(4-(5-methoxy-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <84> (2R,3R,4S,5S)-2-((4'-methoxy-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol, <85> (2R,3R,4S,5S)-2-(4-(6-methoxypyridin-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <86> (2R,3R,4S,5S)-2-((4'-isopropyl-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol, <87> (2S,3R,4S,5S)-2-((4'-isopropyl-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol, <88> (2R,3R,4S,5S)-2-(4-(6-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <89> (2S,3R,4S,5S)-2-(4-(6-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <90> (2R,3R,4S,5S)-2-(4-(5-methyl-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <91> (2R,3R,4S,5S)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <92> (2S,3R,4S,5S)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <93> (2R,3R,4S,5R)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <94> (2S,3R,4S,5R)-2-(4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <95> (2R,3R,4S,5S)-2-(4-(6-ethylbenzofuran-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <96> (2S,3R,4S,5S)-2-(4-(6-ethylbenzofuran-3-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <97> (2R,3R,4S,5S)-2-(3-(7-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <98> (2S,3R,4S,5S)-2-(3-(7-isopropylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <99> (2R,3R,4S,5S)-2-(2-chloro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <100> (2S,3R,4S,5S)-2-(2-chloro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <101> (2R,3R,4S,5R)-2-(2-fluoro-4-(4-isopropylphenoxy)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <102> (2S,3R,4S,5S)-2-(2-chloro-4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <103> (2R,3R,4S,5S)-2-(2-chloro-4-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <104> (2S,3R,4S,5S)-2-(2-fluoro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <105> (2R,3R,4S,5S)-2-(2-fluoro-4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <106> (2S,3R,4S,5S)-2-(3-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <107> (2R,3R,4S,5S)-2-(3-(5-methoxybenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <108> (2S,3R,4S,5S)-2-(4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <109> (2R,3R,4S,5S)-2-(4-(5-methylbenzo[d]oxazol-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <110> (2R,3R,4S,5S)-2-(4-phenethylphenoxy)tetrahydro-2H-pyran-3,4,5-triol, <111> (2R,3R,4S,5S)-2-(4-((E)-styryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <112> (2R,3R,4S,5S)-2-(4-(bis(4-methoxyphenyl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <113> (2R,3R,4S,5S)-2-((4'-(4-isopropylbenzyl)-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol, <114> Furan-2-yl(4-(((2S,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone, <115> Furan-2-yl(4-(((2R,3R,4S,5S)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone, <116> (2R,3R,4S,5S)-2-(4-(4-methoxyphenethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <117> (2R,3R,4S,5S)-2-(4-(4-isopropylphenethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <118> (2R,3R,4S,5S)-2-(4-((E)-4-methoxystyryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <119> (2R,3R,4S,5S)-2-(4-((E)-4-isopropylstyryl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <120> (2R,3R,4S,5S)-2-(4-(benzo[d][1,3]dioxol-5-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <121> (2R,3R,4S,5S)-2-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, <122> (2R,3R,4S,5S)-2-((4'-chloro-[1,1'-biphenyl]-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol, <123> (2R,3R,4S,5S)-2-((4''-isopropyl-[1,1':4',1''-terphenyl-4-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol, <124> (2R,3R,4S,5S)-2-(3-(phenylethynyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol.

18. In any one of paragraphs 1 to 17, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that it has a brain nerve regeneration and protection function by targeting GPCR T1R3.

19. In paragraph 18, A compound, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof, characterized in that it is used for the prevention or treatment of degenerative brain diseases.

20. A pharmaceutical composition for preventing or treating a degenerative brain disease, comprising a compound according to any one of claims 1 to 17, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof.

21. In paragraph 20, A pharmaceutical composition for preventing or treating degenerative brain diseases, characterized by having a brain nerve regeneration and protection function by targeting GPCR T1R3.

22. In paragraph 20, A pharmaceutical composition for preventing or treating a degenerative brain disease, characterized in that the above degenerative brain disease is at least one selected from the group consisting of stroke, dementia, Parkinson's disease, dizziness, epilepsy, peripheral neuromuscular disease, brain tumor, brain lesion disorder, brain edema, paralysis, meningitis, encephalitis, concussion, pituitary tumor, Huntington's disease, tuberculous meningitis, ataxia, mad cow disease, glioblastosis, agoraphobia, cluster headache syndrome, amnesia, Dandy-Walker syndrome, Tourette syndrome, Wernicke-Kosikoff syndrome, meningioma, and Gerstmann syndrome.

23. A food composition for preventing degenerative brain diseases, comprising a compound according to any one of claims 1 to 17, an isomer, a hydrate, a solvate, a prodrug, or a pharmaceutically acceptable salt thereof.