MX2007008489A - Spiroketal derivative and use thereof as diabetic medicine. - Google Patents

Abstract

Disclosed is a compound represented by the following formula (I). [Chemical formula 1] (I) (In the formula, R¹, R², R³ and R⁴ independently represent a hydrogen atom, an optionally substituted C₁-C₆ alkyl group, an optionally substituted C₇-C₁₄ aralkyl group or -C(=O)Rx; Rx represents an optionally substituted C₁-C₆ alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted C₁-C₆ alkoxy group or -NReRf; Ar¹ represents an optionally substituted aromatic hydrocarbon ring or an optionally 1-substituted aromatic heterocycle; Q represents -(CH₂)_m-(L)_p- or -(L)_p-(CH₂)_m-; m represents an integer of 0-2; n represents 1 or 2; p represents 0 or 1; L represents -O-, -S- or -NR⁵-; and A represents an optionally substituted aryl group or an optionally substituted heteroaryl group.) Also disclosed are a prodrug of such a compound, a pharmaceutically acceptable salt of them, a pharmaceutical product or pharmaceutical composition containing such a compound, and the like.

Description

DERIVATIVE OF ESPIROCETAL AND USE OF THE SAME AS A MEDICINE FOR DIABETES TECHNICAL FIELD The present invention relates to pharmaceutically useful spirocetal derivatives, prodrugs thereof and pharmaceutically acceptable salts thereof Particularly, the present invention relates to spirocetal derivatives and prodrugs thereof and salts thereof, which are useful as agents Therapeutic or prophylactic for hyperglycemia-induced diseases such as diabetes including insulin dependent diabetes mellitus (type I diabetes) and non-insulin dependent diabetes mellitus (type II diabetes), diabetic complications and obesity, due to its ability to inhibit -transporter of Na + -glucose 2 (SGLT2) TECHNICAL BACKGROUND In recent years, the number of diabetic patients has increased due to Western diets and a chronic lack of exercise, etc. In diabetic patients, conical hyperglycemia causes reductions in both insulin secretion and insulin sensitivity, which in turn will cause elevation of blood glucose levels and leads to exacerbation of symptoms Drugs conventionally used as therapeutic agents for diabetes include biguanides, sulfonylureas, glycosidase inhibitors and insulin resistance enhancing agents. However, collateral adverse effects of these drugs have been reported, for example, lactic acidosis for biguanides. , hypoglycemia for sulfonylureas, and diarrhea for ghcosidase inhibitors It is now strongly desired to develop therapeutic agents for diabetes that depend on a new mechanism of action that is different from those conventionally proposed. It is reported that flopdzine, a naturally occurring glucose derivative, produces a hypoglycemic effect by inhibiting the sodium-dependent glucose co-transporter 2 (SGLT2) present in the S1 site of the renal proximal tubules resulting in the inhibition of excessive glucose reabsorption in the kidney and in accelerating glucose excretion ( see document that is not paten 1) Up to now, an increasing number of studies have been conducted to develop therapeutic agents for diabetes that depend on the inhibition of SGLT2. For example, compounds used as inhibitors of SGLT2 are reported in JP 2000-080041 A (patent document 1), international publication No WO01 / 068660 (patent document 2), international publication No WO04 / 007517 (patent document 3), etc. However, flopdzine and the compounds described in these patent applications have a problem in that, When administered orally, they are easily hydrogenated by the action of glycosidase or the like present in the small intestine, and therefore rapidly lose their pharmacological effects. Moreover, in the case of flopdzine, its ag with floretma is reported to strongly inhibit sugar transporters of the facilitated diffusion type. For example, there is a report that shows that floretine has an adverse effect of reducing intracerebral glucose levels when administered intravenously to rats (see, v. G, document that is not patent 2) For these reasons, they have been made Attempts to convert these compounds into their prodrug forms in order to avoid said digestion problems and improve the absorption efficiency However, although it is desired that the prodrugs when administered are metabolized in precise form in active compounds in or near their effects stable on target organs are often difficult to achieve due to the action of vain metabolic enzymes present In the body and large variations among individuals, other attempts have also been made to replace the cosidic bonds in these compounds with carbon-carbon bonds (see patent documents 4 to 8). However, the need for demand for further improvements persists. its pharmaceutical properties, including activity and metabolic stability Patent Document 1 Japanese Patent Publication 2000-080041 A Patent Document 2 International Publication No WO01 / 068660, pamphlet Patent document 3 international publication No WO04 / 007517, pamphlet Patent document 4 US patent publication 2001/041674 AA patent document 5 US patent publication 2002/137903 Patent document 6 international publication No WO01 / 027128 pamphlet Patent document 7 international publication No WO02 / 083066, pamphlet Patent document 8 international publication No WO04 / 0131 1, pamphlet Document that is not patent 1 J Clin Invest 93, 397 (1994) Document that is not patent 2 Stroke, 14, 388 (1983) DETAILED DESCRIPTION OF THE INVENTION Problems to be Resolved by the Invention An object of the present invention is to provide a spirocetal derivative having pharmaceutically preferred properties. Particularly, the present invention has the purpose of providing a spiroketal derivative having a hypoglycemic effect and also having pharmaceutically preferred properties such as prolonged efficacy, stability or metabolic safety Another object of the present invention is to provide a pharmaceutical composition used for the prevention or treatment of hyperglycemia-induced diseases such as diabetes including insulin-dependent diabetes mellitus (type I diabetes) and diabetes mellitus not dependent on insulin (type II diabetes), diabetic complications and obesity Measure to solve the problems As a result of extensive and intensive efforts to achieve the objects set forth above, the inventors of the present invention have found that a spiroketal derivative of the formula (I) has excellent inhibitory activity against SGLT2 This finding led to the conclusion of the present invention Namely, in accordance with one aspect of the present invention, a compound of the formula (I) is provided where R, R, R) 3. Y. D R4 are each selected independently of a hydrogen atom, a C1-C6 alkyl group which can be substituted with one or more Ra, an aralkyl group of C7-C4 which can be substituted with one or more Rb, and -C (= O) Rx, Rx represents an alkyl group of Ci-Cß which can be substituted with one or more Ra, an aplo group that can be substituted with one or more Rb, a heterolalk group that can be substituted with one or more Rb, an alkoxy group of C Cß which can be substituted with one or more Ra, or - NReRf, Ar 1 represents an aromatic carbocyclic ring that can be substituted with one or more Rb, or an aromatic heterocyclic ring that can be substituted with one or more Rb, Q represents - (CH2) m- (L) p- or - (L) p- (CH2) m- m represents an integer selected from 0 to 2, n represents an integer selected from 1 and 2, and p represents an integer selected from 0 and 1, L represents -O-, -S- or -NR5-, R5 is selected from a hydrogen atom, an alkyl group of C? -C6 which can be substituted with one or more Ra, and -C? (= O) Rx, A represents an aplo group that can be substituted with one or more Rb or a hetero-group which can be substituted with one or more Rb, wherein the aplo group or the hetero-group can form a fused ring together with the aromatic carbocyclic ring or the aromatic heterocyclic ring, Ra is independently selected from a halogen atom, a hydroxyl group, a cyano group, a nitro group, a carboxyl group, a C6 alkoxy group which can be substituted with one or more Rc, an aplo group that can be substituted with one or more Rd, an aploxy group that can be substituted with one or more Rd, a heterolalk group that can be substituted with one or more Rd, a heteroaploxy group which can be substituted with one or more Rd, a mercapto group, an alkylthio group of C Cß which can be substituted with one or more Rc, an alkylsulfinyl group of C C6 which can be substituted with one or plus Rc, an alkylsulfonyl group of C-pCß which can be substituted with one or more Rc, -NRfRg, an alkoxycarbonyl group of CrC6 which can be substituted with one or more Rc, and an alkylcarbonyl group of C Ce which can be substituted with one or more Rc, Rb is independently selected from an alkyl group of Cr C6 which can be substituted with one or more Rc, a C3-C8 cycloalkyl group which can be substituted with one or more Rc, a C2-C6 alkenyl group which can be substituted with one or more Rc, a C2-C2 alkynyl group which can be substituted with one or more Rc, a C7-C14 aralkyl group which can be substituted with one or more Rd, a halogen atom, a hydroxyl group, a cyano group, a nitro group, a carboxyl group, a C Cß alkoxy group which can be substituted with one or more Rc, an aplo group which can be substituted with one or more Rd, an aploxy group which can be substituted with one or more Rd, a heteropole group which can be substituted with one or more Rd, a heteroaploxy group which can be substituted with one or more Rd, a mercapto group, an alkylthio group of C Cß which can be substituted with one or more Rc, an alkyl group lsulfinyl of C? -C6 which can be substituted with one or plus Rc, an alkylsulfonyl group of C Ce which can be substituted with one or more Rc, -NRfRg, an alkylcarbonyl group of CrCβ which can be substituted with one or more Rc, a C Cβ alkoxycarbonyl group which can be substituted with one or more Rc, a C1-C3 alkylenedioxy group, a heterocyclic group, and a heterocyclyloxy group, Rc is independently selected from a halogen atom, a hydroxyl group, a cyano group, a nitro group, a carboxyl group, an alkoxy group of CrC6, an aplo group that can be substituted with one or more Rd, an aploxy group that can be substituted with one or more Rd, a heterolalk group that can be substituted with one or more Rd, a heteroaploxy group that can be substituted with one or more Rd, an amino group, an alkylamino group of C Ce, and a d? - (alk? lam? no of C C?) group, Rd is independently selected from an alkyl group of C Ce which can be substituted with one or more halogen atoms, an aralkyl group of C7-C, a halogen atom or, a hydroxyl group, a cyano group, a nitro group, an amino group, an alkylamino group of Ci-Cß, and a di- (C 1 -C 6 alkylamino group), Re represents a hydrogen atom, an alkyl group of C? -C6 which can be substituted with one or more Rc, an aplo group which can be substituted with one or more Rd, or a heterolalk group which can be substituted with one or more Rd, Rf represents a hydrogen atom or a C6 alkyl group which can be substituted with one or more Rc, and Rg represents a hydrogen atom, a C6 alkyl group which can be substituted with Rc, a C6 alkylcarbonyl group which can be substituted with one or more Rc, an aplo group which can be substituted with one or more Rd, a heteroatlo group which can be substituted with one or more Rd, a carbamoyl group, an alkoxycarbonyl group of CrCe which can be substituted with one or more Rc, or an alkylsulfonyl group of C Cß which can be substituted with one or more Rc, or and Rf, or Rf and Rg can form a 4- to 7-membered heterocyclic ring together with the nitrogen atom to which they are attached, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. In accordance with another aspect of the present invention , a compound of the formula (la) is provided (la) wherein Ar1, Q, n, R1, R2, R3, R4 and A are as defined above, or a prodrug thereof, or a pharmaceutically acceptable salt thereof In the present invention, Ar1 is preferably a ring of benzene or a thiophene ring (each of which can be substituted with one or more Rb) Likewise, m is preferably 1, and n is preferably 1 Moreover, R1, R2, R3 and R4 are each independently selected from a hydrogen atom and -C (= O) Rx, and Rx is preferably a C6 alkyl group which can be substituted with one or more Ra, or a C6 alkoxy group which can be substituted with one or more Ra In a preferred substitution mode, Ar1 has a substituent - (CH2) mA in its ring atom which is 2 atoms apart from the ring atom directly attached to the substituted glucitol group For example, when Ar1 is a benzene ring, a meta-substituted form is preferred, when Ar1 is a pipdin ring, a 2.4 form -sust? tu? da, 3,5-sust? tu? da or 2,6-sust? tu? da is preferred Alternatively, when Ar1 is a thiophene ring, a 2.5-substituted or 3.5- sust? tu? da is preferred The substituted glucitol group and the substituent - (CH2) mA can be attached to a ring nitrogen atom In accordance with another aspect of the pre In this invention, a compound of the formula (Ib) is provided OP3 (Ib) wherein n represents an integer selected from 1 and 2, Ar1 represents an aromatic carbocyclic ring that can be substituted with one or more Rb, or an aromatic heterocyclic ring which can be substituted with one or more Rb, W represents -OZ or a halogen atom, Z represents a hydrogen atom, an acyl group or a benzyl group, P1, P2 , P3 and P4 are each independently selected from a hydrogen atom, an acyl group or a benzyl group, and R is as defined above This compound is useful, for example, as a synthetic intermediate for the compound of the present invention represented by the formula (I) As used herein, the term " acyl group "is a common name for groups represented by RCO- and encompasses a formyl group, an alkylcarbonyl group of Ci-Cß (vgr, an acetyl group, a propionyl group), an aplcarbonyl group (vgr, a benzoyl group, a naphthoyl group), an aralkylcarbonyl group of C-C14 (v. g, a benzylcarbonyl group), etc. In accordance with yet another aspect of the present invention, a pharmaceutical composition is provided for use as an inhibitor of Na + co-transporter. -glucose, comprising a compound of the formula (I) or (a) above or a prodrug thereof, or a pharmaceutically acceptable salt thereof In accordance with yet another aspect of the present invention, a pharmaceutical composition is provided for to be used in the prevention or treatment of diabetes (v gr, insulin-dependent diabetes mellitus (type I diabetes) or non-insulin-dependent diabetes mellitus (type II diabetes)) or hyperglycemia, diabetic complications induced thereby, or obesity, comprising a compound of the formula (I) or (a) above or a prodrug thereof, or a pharmaceutically acceptable salt thereof. In accordance with yet another aspect of the present invention, a method is provided for the prevention or treatment of diabetes (v. gr., insulin-dependent diabetes mellitus (type I diabetes) or non-insulin-dependent diabetes mellitus (type II diabetes). ), diabetic complications induced by hyperglycemia or obesity, which comprises administering to a patient a therapeutically effective amount of a compound of the above formula (I) or a prodrug thereof, or a pharmaceutically acceptable salt thereof. In formulas (I) and (a) above, groups defined as R 1, R 2, R 3 and R 4 include, for example, a hydrogen atom, a C 6 alkyl group, a C 6 alkoxy alkyl group, and ? -C6, an aralkyl group of C7-C? 4, an alkylcarbonyl group of C? -C6, a aralkylcarbonyl group of C7-C? 4, a C6 alkoxycarbonyl group, and an aralkyloxycarbonyl group of C -d These groups they can be substituted with one or more substituents which are each independently selected from a halogen atom, a hydroxyl group, a C-C alkoxy group, a C-C6 alkylcarbonyl group, a carboxyl group, an amino group and a group amino-substituted, preferably each independently selected from an alkylcarbonyl group of C Ce A hydrogen atom is particularly preferred In formulas (I) and (a) above, Ar 1 can be substituted with the same or different 1 to 4 substituents, for example, each being independently selected from a halogen atom, a hydroxyl group, a C 6 alkyl group, a C3-C8 cycloalkyl group, a Ci-Ce alkoxy group and a C? -C6 alkylthio group (these 4 groups can be substituted with 1 to 4 substituents selected from a halogen atom, a hydroxyl group and an amino group) ), a methylenedioxy group, a cyano group an alkylsulfonyl group of C C6, an alkylsulfonylamino group of C ^ Ce, a nitro group a carboxyl group, an amino-substituted group, and a heteroocichlo group of 4 to 6 members Among the defined groups as Ap, the aromatic carbocyclic ring preferably refers to an aromatic carbocyclic ring containing 5 to 6 carbon atoms, including a benzene ring The aromatic heterocyclic ring preferably refers to an aromatic heterocyclic group of 5 to 6 members, including a pyrrole ring, a thiophene ring, a furan ring, a pipdin ring, a tlazole ring, an isothiazole ring, a pyrazole ring, an indazole ring, an oxazole ring, an isoxazole ring, an imidazole ring, a tpazol ring, a pipmidine ring, an updina ring, a pyrazine ring and a pipdazine ring. Among them Ar1 is preferably a benzene ring, a pyrrole ring, a ring of thiophene, a furan ring or a pyrazole ring, and most preferably a benzene ring, a thiophene ring or a pyrazole ring In the formulas (I) and (a) above, A can be substituted with the same or different 1 to 3 substituents, for example, which are each independently selected from a halogen atom, a hydroxyl group, a C6 C alkyl group , a C3-C8 cycloalkyl group, a C6 alkyloxy group and an alkylthio group of d-Cß (these 4 groups can be substituted with 1 to 4 substituents each independently selected from a halogen atom or a hydroxyl group or an amino group), a methylenedioxy group, a cyano group, an alkylsulfonyl group of C Cß, an alkylsulfonylamino group of CrC6, a nitro group, a carboxyl group, an amino-substituted group, a heteroaryl group of 5 or 6 members, and a heterocyclic group of 4 to 6 members Groups defined as A include, for example, a phenyl group, a naphthyl group, an azulenyl group, a pyrrolyl group, an indolyl group, a pipdyl group, a quinonoyl group, an isoquinolinyl group, a thienyl group, a benzothienyl group, a fuplo group, a benzofuranyl group, a thiazolyl group, a benzothiazole group, a isothiazolyl group, a benzoisothiazolyl group, a pyrazole group, an indazole group, an oxazo group, a benzoxazole group, an isoxazolyl group, a benzoisoxazole group, an imidazolyl group, a benzoimidazole group, a tpazolyl group, a group benzotpazohlo, a pipmidinyl group, an updyl group, a pyrazinyl group, a pipdazinyl group, an imidazopipdyl group, a tpazolopipdyl group and a pyrrolopipdyl group Preferred are a phenyl group, a naphthyl group, a thienyl group, a benzothienyl group, a fuplo group and a benzofuranyl group, and very Preferred are a phenyl group, a thienyl group and a benzothienyl group. As used herein, the term C-alkyl group "C" refers to a linear or branched alkyl group containing 1 to 6 carbon atoms. Examples include methyl, ethyl, -propyl, i-propyl, n-butyl, s-butyl, i-butyl, t-butyl, n-pentyl, 3-methyl butyl, 2-methyl butyl, 1-methyl-butyl , 1-ethylpropyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3-ethylbutyl Preferred C-alkyl groups are, for example, linear or branched alkyl groups containing 1 to 3 carbon atoms, with methyl and ethyl being particularly preferred. As used herein, the term "C2 alkenyl group" is preferred. -C6"refers to a linear or branched alkenyl group containing 2 to 6 carbon atoms Examples include ethenyl (vinyl), 1 -propene, 2-propenyl (aillo), propen-2-? Lo and 3 -buten? lo (homoalyl) As used herein, the term "C2-C6 alkynyl group" refers to a linear or branched alkyl group containing 2 to 6 carbon atoms Examples include ethynyl, 1 -propylene, 2-propylene, 1-butyl, 2-butyl, and 3 -but? n? I As used herein, the term "cycloalkyl group C3-C8" refers to a cyclic alkyl group containing 3 to 8 carbon atoms Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl As used herein, the term "Ci-Ce alkoxy group" refers to an alkyloxy group whose linear or branched alkyl portion containing 1 to 6 Examples carbon atoms include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, i-butoxy, t-butoxy, n-pentoxy, 3-meth? lbutox ?, 2-meth? lbutox? , 1-methylbutoxy, 1 -et? Lpropox ?, n-hexyloxy, 4-met? Lpentox ?, 3-met? Lpentox ?, 2-methylpentoxy, 1 -met? Lpentox? and 3-et? lbutox? As used herein, the term "C7-C14 aralkyl group" refers to an aplakyl group containing 7 to 14 carbon atoms, which contains an aplo group. Examples include benzyl, 1 -fenetyl, 2-phenethi , 1-naphthylmethyl and 2-naphthylmethoxyl As used herein, the term "C7-C14 aralkyloxy group" refers to a 7 to 14 carbon atom containing a dexalkyloxy group, which contains the aralkyl group already defined Examples include benzyloxy, 1-phenethyloxy, 2-phenet? lox ?, -naft? lmet? lox? and 2-naft? lmet? lox? As used herein, the term "aplo group" refers to an aplo group having an aromatic hydrocarbon ring containing 6 to 10 carbon atoms. Examples include phenyl, 1-naphthyl and 2-naphthyl. As used herein, the term "heteroaplo group" refers to a heterocíc co group of 5 to 10 members containing one or more heteroatoms independently selected from oxygen atom, a nitrogen atom and a sulfur atom Examples include fuplo, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, tiadiazo it, tpazohlo, tetrazolyl, pipdinilo, pipmidinilo, pyrazinyl, pipdazinilo, indolyl, quinolmilo and isoquinolinyl heteroaplo groups preferred are cyclic heteroaplo groups 5 to 6 members such as a fuplo group, a group pyrazole, a thienyl group and a pipdinyl group, with a thienyl group being particularly preferred. As used herein, the term "aploxy group" refers to an aploxy group of which the defined aromatic hydrocarbon group containing 6 to 10 carbon atoms Examples include phenoxy, 1 -naftox? and 2-naftox? As used herein, the term "group heteroaploxi" refers to a heteroaploxi group whose heteroaplo portion is the aromatic heterocyclic group of 5 to 10 members as defined containing one or more heteroatoms selected from an oxygen atom, a nitrogen atom and a sulfur atom fuploxi examples include, thienyloxy, Loxi pirro, imidazohloxi, pyrazolyloxy, oxazoltloxi, Loxi isoxazo, Loxi thiazo, isottazoliloxi, Loxi oxadiazo, Loxi tiadiazo, tpazoliloxi, tetrazohloxi, pipdiniloxi, pmmidiniloxi, pyrazinyloxy, pipdaziniloxi, indolyloxy, quinolinyloxysand isoquininoyloxy Preferred hetero-aphoxy groups are 5-6-membered hetero-pyoxy groups As used herein, the term "C 6 -alkylamino group" refers to an alkylamino group whose alkyl portion is a linear or branched alkyl group containing 1 to 6 carbon atoms Examples include methylamino, ethylamino, n-propylamino, i-propylamino, n-butylammo, s-butylamino,? -but? Lam? No, t-butylamino n-pentylamino 3-met? Lbut? Lam? No, 2-met? Lbut? Lam? No, 1 -met? Lbut? Lam? No, 1 -et? Lprop? Lam? No n-hexylamino, 4-met? Lpent? Lam? No, 3-methylpentylamino, 2-met ? lpent? lam? no, 1 -met? lpent? lam? no, 3-et? lbut? lam? no and 2-etilbutilamino As used herein, the term "d? - (C? -C6) amino group" refers to a dialkylamine group whose two alkyl portions are the same or different linear or branched alkyl groups containing 1 to 6 atoms Examples of the "d? - (CrC6 alkyl) amine" group include dimethylamino, diethylamino, di-n-propylamino, di-i-propylamino, di-n-butylamino, methyl-n-butylamino, methyl -s-butylamino, methyl-i-butylamino, methyl-t-butylamine, ethyl-n-butylamino, ethyl-s-butylamine, ethyl-i-butylamino and ethyl-t-butylamino. As used herein, the term "alkylthio group" C-C "refers to an alkylthio group whose alkyl portion is a linear or branched alkyl group containing 1 to 6 carbon atoms Examples include methylthio, ethylthio, n-propylthio, i-propylthio, n-butylthio, s-butylthio, i-butylthio, t-butylthio, n-pentthylthio, 3-methylbutylthio, 2-methyl-butyl, 1-methyl-butyl, 1-ethylpropyl, n-hexylthio, 4-methylpentylthio, 3-met? Lpent? Lt? O, 2-met? Lpent? Lt? O, 1 -met? Lpent? Lt? O, 3-et? Lb U. and 2-ethylbutylthio As used herein, the term "C-alkylsulfinyl" refers to an alkylsulfinyl group (-SO-R) whose alkyl portion is a linear or branched alkyl group containing 1 to 6 carbon atoms. carbon Examples include methylsulfinyl, ethylsulfyl, n-propylsulfinyl, i-propylsulfinyl, n-butylsulfinyl, s-butylsulfinyl, i-butylsulfinyl, t-butylsulfinyl, n-pentylsulfinyl, 3-methyltulphulfinyl, 2-methyltbutyl ? lsulf? n? lo, 1 -met? lbut? lsulf? n? lo, 1 -et? lprop? lsulf? n? lo, n-hexilsulfinilo, 4-methylpentilsulfinilo, 3-met? lpent? lsulf? n? lo , 2-rnet? Lpent? Lsulf? N? Lo, 1-methylpentylsulfinyl, 3-et? Lbut? Lsulf? N? Lo and 2-et? Lbut? Lsulf? N? Lo As used here, the term "alkylsulfonyl group of C Ce "se refers to an alkylsulfonyl group whose alkyl portion is a linear or branched alkyl group containing 1 to 6 carbon atoms Examples include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, i-propylsulfonyl, n-butylsulfonyl, s-butylsulfonyl, i-butylsulfonyl, t -butylsulfonyl, n-pentylsulfonyl, 3-methylbutylsulfonyl, 2-methylt-sulphonyl, 1-methyl-l-sulphonyl, 1-ethylpropyl-sulfonyl, n-hexylsulfonyl, 4-methylpentyl ? sulfonyl, 3-met? lpent? sulfonyl, 2-methylpentylsulfonyl, 1-methylt? l? sulfonyl, 3-et? lbut? l sulfonyl and 2-ethylbutylsulfonyl. As used herein, "-C (= O) -Rx "embraces an alkylcarbonyl group of C Cß, an aralkylcarbonyl group of C7-C? 4 an alkoxycarbonyl group of C Cs, an aralkyloxycarbonyl group of C7-C? and the like Examples of a C 1 -C 6 alkylcarbonyl group include an acetyl group, a propionyl group, a butyl group and a pivaloyl group, an acetyl group being particularly preferred. Examples of a C 7 -C 4 aralkylcarbonyl group include a benzylcarbonyl group and a naphthylmethylcarbonyl group, with a benzylcarbonyl group being preferred. Examples of a C 6 alkoxycarbonyl group include a methoxycarbonyl group and an ethoxycarbonyl group, with a methoxycarbonyl group being preferred. Examples of an aralkyloxycarbonyl group of C -C 4 include a benzyloxycarbonyl group and a group naphthylmethyloxycarbonyl, with a benzyloxycarbonyl group being preferred. As used herein, the term "halogen atom" encompasses a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and Similar As used herein, the term "4- to 7-membered heterocyclic ring" refers to a heterocyclic ring that can be completely saturated or partially or completely unsaturated and that contains a nitrogen atom and can also contain one or more independently selected heteroatoms of an oxygen atom, a nitrogen atom and a sulfur atom Examples include azetidine, pyrrolidine, pipendine and morpholm, with pipepdine being particularly preferred. As used herein, the term "aromatic carbocyclic ring" refers to an aromatic carbocyclic ring of 6. to 10 members Examples include a benzene ring and a naphthalene ring As used herein, the term "aromatic heterocyclic ring" refers to a 5-6 membered aromatic heterocyclic ring containing one or more heteroatoms independently selected from an atom of oxygen, a nitrogen atom and a sulfur atom Examples include a pyrrole ring, an indole ring, a thiophene ring, a benzothiophene ring, a furan ring, a benzofuran ring, a pipdin ring, a ring of quinoline, an isoquinoline ring, a tlazole ring, a benzothiazole ring, an isothiazole ring, a benzoisothiazole ring, a pyrazole ring, an indazole ring, an oxazole ring, a benzoxazole ring, a ring of isoxazole, a benzoisoxazole ring, an imidazole ring, a benzoimidazole ring, a tpazol ring, a benzotpazole ring, a pipmidine ring, a pipmidine ring, a ring of updina, a pyrazma ring and a pipdazine ring As used herein, the term "substituted amimo group" embraces -NreRf, wherein Re represents a hydrogen atom, an alkyl group of CrC6, an alkylcarbonyl group of C6, carbamoyl or an alkoxycarbonyl group of CrCe, and Rf represents a hydrogen atom or a C6 alkyl group, or Re and Rf can form a 4- to 7-membered heterocyclic ring together with the nitrogen atom to which they are attached, and the like As used herein, the term "C 1 -C 3 alkyleneoxy group" refers to a divalent group represented by the formula -O- (d-C 3 alkylene) -O- Examples include a methylenedioxy group, an ethylenedioxy group and a dimethylmethylenedioxy group. As used herein, the term "heterocyclyl group" refers to a 4- to 7-membered heterocyclic group which may be fully saturated or partially or completely unsaturated and which contains one or more heteroatoms independently selected from an atom of oxygen, a nitrogen atom and a sulfur atom Examples include azetidinyl pyrrohydinyl, piperazinyl, piperazinyl, pyrrolyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, oxazolinyl, morpholinyl, thiomorpholinyl, pipdinyl, pyrazinyl, pipmidinyl, pipdazinyl, hexamethyleneimino, fuplo, tetrahydrofuplo , thienyl, tetrahydrothienyl, dioxolanyl, oxathiolanyl and dioxanyl Said heterocyclic group can be substituted at any suitable position on this carbon or nitrogen atom (s). As used herein, the term "heterocyclyloxy group" refers to an oxy group attached to a 4- to 7-membered heterocyclic ring which can be fully saturated or partially or completely unsaturated and which contains one or more heteroatoms independently selected from an oxygen atom, a nitrogen atom and a sulfur atom Examples include azetidinyloxy , pirrohdiniloxi, pipepdmiloxi, piperazíniloxi, pyrrolyloxy, imidazolyloxy, imidazoliniloxi, pirazohloxi, pirazoliniloxi, oxazo niloxi, morfoliniloxi, tiomorfoliniloxi, pipdiniloxi, pyrazinyloxy, pipmidiniloxi, pipdaziniloxi, hexametileneiminoxi, funloxi, tetrahidrofuploxi, thienyloxy, tetrahidrotieniloxi, dioxolaniloxi, oxatiolaniloxi and díoxaniloxi said heterocyclic group can be substituted for any substitutable position in its carbon or nitrogen atom (s) The compound of the present invention also includes mixtures or isolated forms of stereoisomeric vanes such as tautomers and optical isomers In some cases, the compound of the present invention The ion can form an acid addition salt Depending on the type of substituent, the compound of the present invention can also form a salt with a base. Specific examples of said salt include acid addition salts with mineral acids (v gr, hydrochloric acid, hydrobromic acid). , acid yodhídpco, sulfuric acid, nitric acid, phosphoric acid), with organic acids (v gr, formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid , tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid) and with Acid amino acids (v gr, formed with a base include salts with inorganic bases (v gr, sodium, potassium, magnesium, calcium, aluminum), salts with organic bases (v gr, methylamine, ethylamine, ethanolamine), salts with basic amino acids ( v. gr, lysine, ornithine), as well as ammonium salts. Furthermore, the compound of the present invention also includes pharmaceutically acceptable hydrates, solvates, and crystalline polymorphic forms, etc. It should be noted that the compound of the present invention is not limited to compounds shown in the examples section described below, and encompasses all the spirocetal derivatives of formula (I) above and their pharmaceutically acceptable salts. Furthermore, the present invention also encompasses so-called prodrugs, ie, compounds that are metabolized in I live to compound the above formula (I) or its pharmaceutically acceptable salts. Examples of prodrug-forming groups for the compound of the prese This invention includes those found in Prog Med vol 5, pp 2157-2161 (1985) and "lyakuhin no Kaihatsu (Development of Pharmaceuticals)" vol 7 (Molecular Design), pp. 163-198, published in 1990 by Hirokawa Publishing Co, Japan The compound of the present invention can be prepared by applying several known synthesis methods, depending on their characteristics based on the skeletal structure or the type of substituent In some cases, depending on the type of functional group, it is technically it is preferable to protect this functional group with a suitable protecting group in the starting material stage or in an intermediate step. In this case, the protecting group can be removed in the subsequent step to obtain a desired compound. For example, a hydroxyl group or a group carboxyl can be given as a functional group required to be protected during the production process. Protective groups for these groups include those found in "Protective Groups in Organic Synthesis" 2nd edition, written by Greene and Wuts The type of protective group that has been Use, as well as the reaction conditions for the introduction and removal of the protecting group may be selected as appropriate based on known techniques as shown in the above document. The compound of the present invention has inhibitory activity against glucose co-transporter. sodium dependent 2 (SGLT2) involved in glucose reabsorption in the barrel (J Cl in Invest, vol 93, p 397, 1994) Inhibition of SGLT2 prevents the reabsorption of sugar and removes excess sugar from the body to thereby produce a therapeutic effect on diabetes and an improving effect on insulin resistance through the Correction of hyperglycemia without applying any load to pancreatic β cells Therefore, in accordance with one aspect of the present invention, a pharmaceutical preparation is provided for the prevention or treatment of diseases or conditions that can be mitigated by the inhibition of SGLT2, v gr, diabetes, related diseases with diabetes and diabetic complications As used herein, the term "diabetes" 'encompasses type I diabetes, type II diabetes and other types of diabetes with specific etiology. Likewise, the term "diabetes-related diseases" includes, for example, obesity , hyperpulsulinemia, abnormal carbohydrate metabolism, hyperlipidemia, hypercholesterolemia, hypertrglicepidemia, abnormal lipid metabolism, hypertension, congestive heart failure, edema, hyperupcemia and gout. As used herein, the term "diabetic complications" includes both acute complications and chronic complications. "Acute complications" include hyperglycemia (v gr, ketoacidosis), infections (v gr, skin infections, soft tissue, biliary system, respiratory system and urinary tract), etc. Examples of "chronic complications" include microangiopathy (v gr, nephropathy , retinopathy), artepoesclerosis (v gr, atherosclerosis, cardiac infarction, infarction cerebral, arterial occlusion of lower extremities), neuropathy (v.gr, sensory nerves, motor nerves, autonomic nerves), gangrene of the feet, etc. Major diabetic complications include diabetic retinopathy, diabetic neuropathy and diabetic neuropathy The compound of the present invention also it can be used in combination with any therapeutic agent for diabetes, diabetic complications, hyperlipidemia or hypertension, which depends on a mechanism of action different from that of inhibition of SGLT2 activity When combined with other drugs, the compound of the present invention can be expected to produce an additive effect on these diseases, which is greater than any other. Examples of a "therapeutic agent for diabetes or diabetic complications" available for combination use include, for example, insulin sensitizers (v gr, PPAR agonists ?, PPARa agonists / ?, PPARd agonists, PPARa agonists /? / d), g cosidase inhibitors, biguanides, insulin secretagogues, insulin formulations, antagonists of glucagon receptor, stimulators of insulin receptor cmasa, inhibitors of tppeptidyl peptidase II, inhibitors of dipeptidyl peptidase IV, inhibitors of protein tyrosine phosphatase-1 B, inhibitors of glycogen phospho-plasin, inhibitors of glucose-6-phosphatase, inhibitors of gluconeogenesis, fructose-bisphosphatase inhibitors, pyruvate dehydrogenase inhibitors, glucococcal activators, D-chiroinositol inhibitors, glycogen synthase c-nase-3, glucagon-like peptide-1, glucagon-like peptide-1 analogs, peptide-1 agonists similar to glucagon, amyna, amynane analogues, amylin agonists, glucocorticoid receptor antagonists, 1-ß-h? drox? estero? dehydrogenase inhibitors, aldose reductase inhibitors, protein kinase C inhibitors, acid receptor antagonists? -aminobutypic, sodium channel antagonists, transcription factor inhibitors NF-B, inhibitors of IKKß, lipid peroxidase inhibitors, N-linked dipeptidase-acetylated acid inhibitors, insulin-like growth factor, growth factors Platelet derivatives (PDGF), analogues of platelet-derived growth factors (PDGF), epidemial growth factors (EGF), nerve growth factors, carnitine derivatives, updma, 5-h? drox? -1 -methylidantoin, EGB-761, bimoclomol, sulodexide, Y-128 and TAR-428 Illustrative examples of a therapeutic agent for diabetes or diabetic complications are the following: "Biguanides" include metformm hydrochloride and fenformm "Insulin secretagogues", include those of the type of sulfonylurea such as g bupda (glibenclamide), ghpizide, g clazide and chlorpropamider as well as those of the non-sulfonylurea type such as nategrida, repaglinide and mitiglinide "Insulin formulations" encompass both recombinantly produced human insulin and insulin derived from animals formulations can be divided into three groups depending on the length of south duration fast-acting formulations (v gr, human insulin, insulin neutr a human), intermediate-acting formulations (v gr, aqueous suspension of human insulin-isophane human insulin, aqueous suspension of human neutral insulin-isophane human insulin, aqueous suspension of human-zinc insulin, aqueous suspension of insulin-zinc), and Long-acting formulations (v gr, human-zinc crystalline insulin suspension) "Glycosidase inhibitors" include acarbose, voglibose and mightol "Insulin sensitizers" include PPAR agonists? such such as troglitazone, pioglitazone and rosiglitazone, dual PPARa agonists /? such as MK-767 (KRP-297), tesaghtazar, LM4156, LY510929, DRF-4823 and TY-51501, as well as PPARd agonists such as GW-501516"Tppeptidyl peptidase II inhibitors" include UCL-139"Dipeptidyl Inhibitors peptidase IV "include NVP-DPP728A, LAF-237, MK-0431, P32 / 98 and TS1 -225"Aldose reductase inhibitors" include ascorbyl gamolenate, toirestat, epalrestat, fidarestat, sorbinil, ponalrestat, risarestat and zenarestat "Acid receptor antagonists? -aminobutipco" include topiramate "Sodium channel antagonists" include mexiletine hydrochloride "NF-? B transcription factor inhibitors" include dexlipotam "Lipid peroxide inhibitors" include tiplazad mesylate "N-acetylated acid-bound dipaptidase inhibitors" include GPI- 5693"Carnitine derivatives" include carnitine and levacecamine hydrochloride Examples of a "therapeutic agent for hyperlipidemia or hypertension" available for combination use include, for example, inhibitors of hydroxymethylglutapl coenzyme A reductase, fibrate, β3-adrenergic receptor agonists, AMPK activators, inhibitors of acyl-coenzyme A cholesterol acyltransferase, probucol, thyroid hormone receptor agonists, cholesterol absorption inhibitors, raisin inhibitors, microsomal-typed transfer inhibitors, lipoxygenase inhibitors, carnitine palmitoyl transferase inhibitors, squalene smtase inhibitors, low density poprotein promoters, nicotinic acid derivatives, bile acid binding resins, sodium-dependent bile acid transporter inhibitors, protein transport inhibitors, cholesterol ester, angiotensin-converting enzyme inhibitors, angiotensin II-converting enzyme antagonists, endothelin-converting enzyme inhibitors, endothelin receptor antagonists, diuretics, calcium antagonists, antihypertensive vasodilators, sympatholytic agents, centrally acting antihypertensive drugs, agonists of a2-adrenergic receptor, antiplatelet agents, uric acid production inhibitors, uric acid excretion stimulators, urinary alkalizers, anorectics, ACE inhibitors, adiponectin receptor agonists, GPR40 agonists and GPR40 antagonists Illustrative examples of a therapeutic agent for hyperhpidemia or hypertension are the following "Inhibitors of hydroxymethylglutapl coenzyme A reductase" include fluvastatin, lovastatin, pravastatin, cepvastatin and pitavastatin "Fibrate compounds" include bezafibrate, beclobrate and binifibrate "Squalene synthase inhibitors" include TAK-475 and a-phosphonosulfonate derivatives (U.S. Patent No. 5,712,396) "Acyl-Coenzyme A Cholesterol Acyltransferase Inhibitors" include CI-101 1, NTE-122, FCE-27677, RP -73163, MCC-147 and DPU-129"Low-density lipoprotein promoters" include MD-700 and LY-295427"Microsomal-typed transfer inhibitors (MTP inhibitors)" include compounds as described in, v. Gr, patents United States Nos. 5739135, 5712279 and 5760246"Anorectics" include adrenahne / noradrenaline agonists (v gr, mazindol, ephedrine), serotonin agonists (selective serotonin reuptake inhibitors such as fluvoxamine), adrenaline / serotonin agonists (v gr, sibutramine), melanocortin 4 receptor agonists (MC4R), hormone concentrators a -melanocytes (a-MCH), leptin, as well as transcripts regulated by cocaine and amphetamine (CART) "Thyroid hormone receptor agonists" include sodium otironin and levothyroxine sodium "Cholesterol absorption inhibitors" include ezetimibe "Raisin inhibitors" include or stat "Camitine palmitoyl transferase inhibitors" include etomoxir "Nicotinic acid derivatives" include nicotinic acid, nicotinamide, nicomol and nicorandil "Bile acid binding resins" include cholestyramine, cholestylan and colesevelam chlorhiodrate "Angiotensin-converting enzyme inhibitors" include captopl, enalappl maleate, alaceppl and cilazappl "Angiotensin II-converting enzyme antagonists" include candesartan cilexetil, losartan potassium and Eprosartan mesylate "Endothelin-converting enzyme inhibitors" include CGS-31447 and CGS-35066"Endothelin receptor antagonists" include 1 -749805, TBC-3214 and BMS-182874 By way of example, in the treatment of diabetes or the like , it would be preferable to use the compound of the present invention in combination with at least one drug selected from the group consisting of an insulin sensitizer (v. g, a PPAR agonist ?, a PPARa agonist / ?, a PPARd agonist, a PPARa /? / d agonist), a glycosidase inhibitor, a biguanide, an insulin secretagogue, an insulin formulation and a dipeptidyl peptidase inhibitor IV Alternatively, it would be preferable to use the compound of the present invention in combination with at least one drug selected from the group consisting of an inhibitor of hydroxymethylglutapl coenzyme A reductase, a fibrate compound, a squalene smtase inhibitor, an acyl Coenzyme A cholesterol acyltransferase, a low density lipoprotein promoter, a transfer inhibitor of tpglicépdos microsomal and an anorectic The pharmaceutical preparation of the present invention can be administered systemically or topically orally or parenterally (v gr, intrarectal, subcutaneous, intramuscular, intravenous, percutaneous). To be used as a pharmaceutical preparation, the compound of the present invention is can be formulated in any desired desired dosage form of solid compositions, liquid compositions and other compositions, as appropriate for the intended purpose. The pharmaceutical preparation of the present invention can be prepared by mixing the compound of the present invention with pharmaceutically acceptable carrier (s). (s) More specifically, the compound of the present invention can be supplemented with excipients, extenders, binders, disintegrating agents, coating agents, sugar coating agents, pH adjusters, solubilizers, aqueous or aqueous solvents, etc. Commonly used, and then formulated using standard techniques in tablets, pills, capsules, granules, powders, solutions, emulsions, suspensions, injections, etc. Examples of excipients and extenders include, for example, lactose, magnesium stearate, starch, talc, gelatin, agar, pectin, gum arabic, olive oil, sesame oil, cocoa butter, ethylene cabbage and other commonly used matepals Also, the compound of the present invention can be modified to form an inclusion compound with, v gr, a- ß- or? - cyclodextrin or methylated cyclodextrin before being formulated The dose of the compound of the present invention will vary depending on the disease or symptom to be treated, body weight, age, sex, route of administration, etc. The dose for adults is preferably 0 1 to 1000 mg / kg of body weight / day, most preferably 0 1 to 200 mg / kg of body weight / day, given as a single dose or in divided doses The compound of the present invention can be synthesized, for example, as it is shown in the following production schemes The compound of the present invention can be synthesized as shown in scheme 1 SCHEME 1 wherein R11 and R12 have the same meaning as defined above for substituents on Ar1, A is as defined above, and P represents a protecting group for a hydroxyl group. More specifically, after the compound (II) is protected with a protecting group P (v g a tptyl group, a tert-butyldimethylsilyl group or a tetrahydropyranyl group, preferably a group removable by the action of an acid), the resulting compound (III) is treated with a lithium-alkyl (vg, n-butyl-lithium, sec-butyl-lithium) and reacted with the compound (IV) to obtain the compound (V) in the presence or absence of a silane reagent (v. gr, tpethylsilane), the compound (V) is then treated with an acid (v gr, tffluoroacetic acid or complex boron trifluoride-diethyl ether) is converted to compound (VI), followed by treatment with an oxidizing agent (v gr , Dess-Martin reagent, TPAP-NMO, DMSO-acetic anhydride) to obtain the compound (VII) This compound is converted to compound (VIII) by treatment with a metal reagent such as a Gpgnard reagent, followed by debenzylation, v gr, through catalytic hydrogenation in the presence of a palladium catalyst or a technique using a Lewis acid (boron tbromide, boron t-chloride, boron t-chloro-dimethylsulfide complex, boron-ether t-phluoride complex diethyl ether plus ethanediol, boron-ether trifluoride complex diethyl plus dimethyl sulfide) to prepare the compound of the present invention It should be noted that the compounds (II) and (IV) can be synthesized as described, for example, in J Org Chem, vol 29, p 2034, 1964 and Carbohydr Res, vol 260, p 243, 1994, respectively. The compound of the present invention can also be prepared as shown in the following scheme 2 SCHEME 2 wherein R 11 and R 2 have the same meaning as defined above for substituents on Ar 1, A is as defined above, X 1 represents a halogen atom, and X 2 represents a halogen atom or B (OR 13) 3, wherein R 13 represents hydrogen or lower alkyl More specifically, the compound (VI) is treated with an appropriate halogenating agent (vgr, N-bromosuccimide, carbon tetrabromide) The resulting compound (IX) is then reacted with the compound (X) in the presence of an appropriate palladium catalyst to obtain the compound (XI), followed by debenzylation, v gr, through catalytic hydrogenation in the presence of a palladium catalyst or a technique using a Lewis acid (boron tbromide, tpchloride boron, boron-dimethyl sulphide complex boron complex, boron trifluoride-diethyl ether plus ethanediol complex, boron trifluoride-diethyl ether complex more dimethyl sulfide) to prepare the compound of the present invention The compound of the present invention can also be prepared as shown in scheme 3 SCHEME 3 on wherein R1 1 and R12 have the same meaning as defined above for substituents on Ar1, R13 represents lower alkyl, A is as defined above, P represents a protective group for a hydroxyl group, and X1 represents a halogen atom. more specific, after the hydroxyl group of the compound (XII) is protected with an appropriate protecting group P (v gr, a t-thyl group, a tert-butyldimethylsiyl group, a tetrahydropyranyl group), the resulting compound (XIII) is treated with an appropriate alkyothio (v, n-butylthio, sec-butyl-thio) and reacted with the compound (IV) to derthe compound (XIV) In the presence or absence of a silane reagent (v gr, tpethylsilane), the compound (XIV) is then treated with an acid (v gr, tffluoroacetic acid or trifluoride complex). of boron-diethyl ether) to derthe compound (XV), followed by treatment with a hexaalkyldistin in the presence of an appropriate palladium catalyst to obtain the compound (XVI) In the presence of an appropriate palladium catalyst, the compound (XVI) is then treated with the compound (XVII) to derthe compound (XI), followed by deprotection to synthesize the compound of the present invention. The compound of the present invention can also be prepared as shown in the following scheme.

SCHEME 4 (XIX) (XX) O (XVIII) 0A .OBn R? 2 R «R12 Bn? lOBn /; OH reduction ,, < ? protection QII_! Í_ 2"/ M ÓBn ÓP ér A ¿H »* (« XI) < »'") (HI "> (XXIV) (?)) wherein R11 and R12 have the same meaning as defined above for substituents on Ar1, A is as defined above, P represents a protecting group for a hydroxyl group, and X represents a halogen atom. The compound (XVIII) is brominated with an appropriate sprouting agent (v.gr, bromine, N-bromosuccimide) and its hydroxyl group is protected with an appropriate protecting group P (e.g., a trityl group, a tertiary group). butyldimethylsilyl, a tetrahydropyranyl group), followed by the use of a Grignard reagent or the like to obtain the adduct (XXI). The resulting hydroxyl group is removed by being treated with a silane reagent (e.g., triethylsilane) in the presence of an acid (e.g., trifluoroacetic acid or boron trifluoride-diethyl ether complex) to derive the compound (XXII ) If necessary, the hydroxyl group is again protected to give the compound (XXIII) The reaction between the compounds (IV) and (XXIII) is carried out in the same manner as shown in scheme 3 for the reaction between the compounds (IV) and (XIII) The conversion of the compound (XXIV) to the compound (XI) is carried out in the same manner as shown in scheme 3 for the conversion of the compound (XIV) into the compound (XV). The compound of the present invention can also be prepared as It is shown in the following scheme 5 SCHEME 5 where R1 1 and R 2 have the same meaning as defined before for substituents on Ar, L, m, p and A are as defined above, and X represents a halogen atom Compound (VI) is debenzylated, v gr, through catalytic hydrogenation in the presence of a palladium catalyst or a technique using a Lewis acid (boron tbromide, boron tbromide, boron tpcloride-dimethyl sulfide complex, boron trifluoride diethyl ether plus ethanethiol complex, boron trifluoride-diethyl ether plus dimethyl sulfide complex ), and the resulting compound (XXV) is treated in a suitable solvent (vgr, dimethyl sulfoxide, dimethylformamide) with a halogenating agent (v. g, tpmethylsilyl chloride, tpmethylsihlo bromide) to obtain the compound (XXVI). that each hydroxyl group is further protected with an appropriate protecting group (vgr, an acetyl group, a tert-butyldimethylsilyl group), the resulting compound (XXVII) is reacted with boronic acid (vg, phenylboronic acid) and n the presence of an appropriate palladium catalyst (v gr, palladium acetate, DPPF), or alternatively, it is reacted with a Gpgnard reagent in the presence or absence of copper chloride, or alternatively, it is reacted with a nucleophilic reagent ( v gr, phenol, aniline, thiophenol) in the presence of a base (v gr, carbonate and potassium) to obtain the compound (XXVIII). This compound can be protected to prepare the compound of the present invention. The compound of the present invention is also You can prepare as shown in the following scheme 6 SCHEME 6 (XXXI) (XXXII) (XXXIV) (XXXIII) wherein R 13 represents an ester group, Ar 1, L, m, p and A are as defined above, P represents a protective group for a hydroxyl group, and X 1 represents a halogen atom in a solvent (v. gr., dimethylformamide), the compound (XXIX) is reacted with a nucleophilic reagent (v.gr, phenol, benzyl alcohol, thiophenol, aniline, benzylamine) in the presence of a base (v.gr, potassium carbonate) to obtain compound (XXX), followed by reduction of ester and protection of the resulting hydroxyl group to obtain the compound (XXXII).

The conversion of the compound (XXXII) to the compound (XXXIV) is carried out from the same way as shown in scheme 4 for the conversion of the compound (XXIII) to the compound (XI) The compound (XXXIV) can bedeprotected to prepare the compound of the present invention The compound of the present invention can also be Prepare as shown in the following scheme 7 SCHEME 7 (XXXV) (XXXVI) (XXXVII) o o A ^ OBn BnO OBn (XXXVIII) (XXXIX) where R »1 1 has the same meaning as defined previously for substituents on Ar1, G represents -O-, -S- or -NP-, P represents a protective group for an amino group, A is as defined before, and X1 represents a halogen atom. The compound (XXXV) is treated with a Gpgnard reagent or the like to give the compound (XXXVI), followed by the use of a reducing agent such as tpethylsilane to obtain the compound (XXXVII). The compound is treated with a base such as LDA and then reacted with oxirane to obtain the compound (XXXVIII), followed by protection of the hydroxyl group to obtain the compound (XXXIX). The conversion of the compound (XXXIX) to the compound (XXXX) is performed in the same manner as shown in scheme 4 for the conversion of the compound (XXIII) to the compound (XI) The compound (XXXXI) can be deprotected to prepare the compound of the present invention The compound of the present invention can also be Prepare as shown in the following scheme 8 SCHEME 8 coupling (XXXXI I) (XXXXIII) (XXXXIV) deprotection (XXXXV) (XXXXVI) wherein R 1 1 has the same meaning as defined above for substituents on Ar 1, A is as defined above, X 1 represents a halogen atom, and P represents a protective group for a hydroxyl group. The compound (XXXXIII), which is prepared by coupling the reaction using the compound (XXXXII), is cyclized and deprotected in the presence of an acid such as p-toluenesulfonic acid to give the compound (XXXXIV). The resulting compound is treated with a halogenating agent (for example, trimethylsilyl chloride, trimethylsilyl bromide and the like) in a suitable solvent (for example, dimethyl sulfoxide, dimethylformamide and the like) to give compound (XXXXV). Subsequently, the compound The resulting product is reacted with boronic acid (for example phenylboronic acid and the like) in the presence of a palladium catalyst (for example, palladium acetate, DPPF and the like) to give the compound (XXXXVI). By deprotection of the resulting compound, it can be produced The compound of the present invention How to prepare the compound of the present invention is not limited to the embodiments illustrated above For example, the compound of the present invention can also be synthesized through any combination of the steps included in schemes 1 to 8 EXAMPLES The present invention will be further described in more detail by the following examples and test examples, which are not intended to limit the scope of the invention. In the following examples, the individual symbols are defined as follows NMR nuclear magnetic resonance spectrum (internal standard TMS) , EM Mass Spectrometry and CLAR High Performance Liquid Chromatography NMR, EM and CLAR are measured using the following NMR instruments JEOL JNM-EX-270 (270 MHz) or Brucker ARX300 (300 MHz) or Vanan Mercury 300 (300 MHz) or JEOL JNM-ECP400 (400 MHz) EM Thermo Finigan LCQ or Waters micromass ZQ or triple quadrupole mass spectrometry Q-micro CLAR Waters 2690/2996 (detector) EXAMPLE 1 1, 1 -Anhydro-1-C-r5- (4-ethylphenyl) methyl-2- (hydroxymethyl) phenan-β-D-glucopyranose 1) Synthesis of (2-bromo-4-h? Drox? Met? Lfen? L) methanol Under a stream of nitrogen, to a solution of 2-bromo-terephthalic acid (5.0 g, 20.4 mmol) in THF (50 ml), a THF solution of BH3 (1 09 M, 74 9 ml) was added dropwise at 0 ° C and the mixture was stirred at room temperature for 4 hours After the addition of THF-water (1 1) to this solution, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography. (developing solution = ethyl acetate n-hexane (1 2)) to give the title compound (4 1 g, 92%) 1 H-NMR (DMSO-de) d 4 48 (4H, t, J = 5 1 Hz), 5 27 (1 H, t, J = 6 Hz), 5 37 (1 H, t, J = 5 7 Hz), 7 31 (1 H, d, J = 7 8 Hz), 7 45-7 49 (2 H, m) MS (ESI +) 240 [M + Na] + 2) Synthesis of 2-bromo-1, 4-b? S (tpt? Lox? Met? L) benzene Under a stream of nitrogen, to a solution of tptyl chloride (1 1 58 g, 41 6 mmoles) and ( 2-bromo-4-hydroxylmethyl) methanol (4 1 g, 18 9 mmol) in DMF (12 ml), tetylamine (5 8 ml, 41 6 mmol) and DMAP (369 2 mg, 3.02 mmol) were added and the mixture was stirred for 18 hours at room temperature. The reaction mixture was evaporated under reduced pressure to remove the solvent and then extracted with methylene chloride. The organic layer was washed with water and aqueous sodium chloride. Saturated, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 2)) to give the title compound (2 4 g, 18%) 1 H-NMR (CDCl 3) d 4 20 (4 H, d, J = 18 Hz), 7 22-7 34 (21 H, m), 7 47-7 53 (12H, m) 3) Synthesis of 3,4,5-tr? S-benz? Lox? -6-benz? Lox? Met? L-2- (2,5-b? S (tpt? Lox? Met? L) phen? l) tetrah? drop? ran-2-ol Under a stream of nitrogen, to a solution of 2-bromo-1,4-b? s (tpt? lox? met? l) benzene (255 3 mg, 0 36 mmol. ) in toluene (1.5 ml), a solution in cyclohexane of sec-butyllithium (0 99 M, 367 μl, 0 36 mmol) was added dropwise at room temperature and the solution was stirred for 30 minutes. added dropwise at -78 ° C to a solution of 3,4,5-tr? sbenc? lox? -6- (benz? lox? met? l) tetrah? drop? ran-2-one (140 mg. 26 mmoles) in toluene (1.5 ml) and the mixture was stirred at the same temperature for 30 minutes. After the addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1.5)) to give the titer (242 mg, 80%) 1 H-NMR (CDCl 3) d 3 34 (1 H, t, J = 9 3 Hz), 3 46-3 51 (3 H, m), 3 78 (1 H, d, J = 10 8Hz), 3 92 (1 H, t, J = 9 3Hz), 4 00-4 05 (1 H, m), 4 08-4 16 (3H, m), 4.31 (2H, s), 4 41 (1 H, d, J = 12 3Hz), 4 49-4 58 (2H, m), 4 77-4 84 (3H, m), 6 75 (2H, d, J = 7 2Hz), 6 95 ( 2H, t, J = 7 2Hz), 7 02-7 07 (1 H, m), 7 11 -7 32 (35H, m), 7 47-7 59 (12H, m), 7 69 (1 H, d, J = 7 5Hz) MS (ESI +) 1 184 [M + Na] + 4) Synthesis of 1, 1 -anh? Dro-1-C- [2,5-b? S (hydrox? Met? L) phen? 1-2, 3,4,6-tetra-O-benz ? l-ß-D-qlucop? ranosa Under a stream of nitrogen, to a solution of 3,4,5-tr? sbenc? lox? -6-benz? lox? met? l-2- (2,5- b? s (tpt? lox? met? l) fen? l) tetrah? drop? ran-2-ol (242 mg, 0 21 mmol) in acetonitoplo (3 ml), tpethylsilane (36 .mu.l, 0.23 mmol) was added. and complex of boron trifluoride-diethyl ether (29 μl, 0 23 mmol) at -40X and the mixture was stirred at the same temperature for 1 hour after stirring at 0 ° C for an additional 1 hour, water was added and the The reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by flash column chromatography. silica gel (developing solution = ethyl acetate n-hexane (14)) to give the title compound (77 5 mg, 56%) 1 H-NMR (CDCl 3) d 3 62-3 71. { (H, d, J = 1 1 1 Hz), 3 77-3 92 (3H, m), 4 07-4 18 (3H, m), 4 40-4 63 (6H, m), 4 83-4 95 (3H, m), 5 17 (2H, s), 6 75 (2H, s), 7 06-7 31 (25H, m) MS (ESI +) 681 [M + Na] + ) Synthesis of 1, 1-anh-dro-1-C-f5-form? L-2- (hydrox? Met? L) phen? L1-2,3,4,6-tetra-O-benc ? l-ß-D-qlucop? ranosa Under a stream of nitrogen, to a solution of 1, 1 -anh? dro-1-C- [2,5-b? s- (h? drox? met? l) phen? l] -2,3,4,6-tetra-O-benzyl-β-D-glucopyranose (77 5 mg, 0 12 mmol) in methylene chloride (15 ml), reagent was added of Peryodinan from Dess-Martm (74 8 mg0.18 mmoles) at room temperature and the mixture was stirred for 30 minutes After the addition of water, the reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over sodium sulfate, Anhydrous magnesium, and then evaporated under reduced pressure to remove the solvent The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 4)) to give the compound of the title (25 2 mg, 33%) 1 H-NMR (CDCl 3) d 3 66 (1 H, d, J = 10 8 Hz), 3 76-3 95 (3 H, m), 4 08-4 1 1 (1 H, m), 4 15-4 27 (2H, m), 4 47 (2H, dd, J = 12, 21 3Hz), 4 65 (2H, d, J = 10 8Hz), 4 88 (1 H, d, J = 10 8Hz), 4 95 (2H, s), 5 24 (2H, s), 6 77 (2H, d, J = 6 9Hz), 7 03-7 15 (3H, m), 7 19-7 41 (18H, m), 7 53 (1 H, s), 7 87 (1 H, d, J = 7 8Hz), 9 85 (1 H, s) MS (ESI +) 679 [M + Na] + 6) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-et? Lfen? L) h? Drox? Met? L-2- (hydro? Met? L) fen? Ll -213,4,6-tetra-O-benzyl-β-D-qlucopranose Under a stream of nitrogen, to a solution of 1, 1 -anh? Dro-1-C- [5-form] -2- (H? Drox? Met? L) phen? L] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose (25 2 mg, 0 038 mmol) in diethyl ether (0 3 ml), a THF solution of 4-et? lfen? lmagnes? or (0 5 M, 153 μl, 0 077 mmol) bromide was added at 0 ° C and the mixture was stirred for 3 days at room temperature After the addition of water, the rm was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 4)) to give the title compound (23 3 mg, 80%) 1 H-NMR (CDCl 3) d 1 13 (3H, t, J = 7 5Hz), 2 53 (2H, q, J = 7 2Hz, J = 7 8Hz), 3 63 (1 H, d, J = 9 9Hz), 3 78-3 90 (3H, m), 4 08-4 1 1 (2H, m), 4 43- 4 64 (4H, m), 4 89 (3H, d, J = 10 2Hz), 5 17 (2H, s), 5 81 (1 H, s), 6 67 (2H, s), 7 00-7 47 (Z 5H, m) 7) Synthesis of 1, 1 -anh? Dro- -C-5- (4-et? Lfen? L) met? L-2- (hydro? Met? L) fen? Ll-2,3,4 , 6-tetra-O-benzl-β-D-qlucopranyose Under a stream of nitrogen, to a solution of 1.1 -anh? Dro-1-C- [5- (4-et? Lfen? l) h? drox? met? l-2- (hydrox? met? l) fen? l] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose (23 3 mg, 0 031 mmol) in acetonitoplo (1 ml), tpethylsilane (5 8 μl, 0 037 mmol) and complex of boron trifluoride-diethyl ether (3 8 μl, 0 031 mmol) were added at -40 ° C and the The mixture was stirred at the same temperature for 2 hours. After the addition of water, the reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1:10)) to give the title compound (18 9 mg, 83% 1H-R MN (CDCI3) d 1 15 (3H, t, J = 7 5Hz), 2 55 (2H, q, J = 7 2, 7 8Hz), 3 63 (1 H, d, J = 9 3Hz), 3 77 -3 81 (1 H, dd, J = 3 6, 3 9Hz), 3 83 (1 H, s), 3 86 (1 H, s), 3 95 (2H, s), 4 00 (1 H, d, J = 10 8Hz), 4 06-4 1 1 (2H, m), 4 47 (2H, d, J = 12Hz), 4 60 (2H, d, J = 12 3Hz), 4 64 (1 H , s), 4 84 (1 H, d, J = 3Hz), 4 89 (2H, d, J = 4 8Hz), 5 17 (2H, dd, J = 5 1, 12 3Hz), 6 71 (2H , d, J = 6 3Hz), 6 96-7 31 (25H, m) MS (ESI +) 769 [M + Naf 8) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-et? Lfen? L) met? L-2- (hydro? Met? L) fen? Ll-b-D -qlucopranose To a solution of 1, 1 -anh? dro-1-C- [5- (4-et? lfen? l) -met? l-2- (hydro? met?) fen? l] -2,3,4,6-tetra-O-benzyl-β-D-glucopyranose (18 9 mg, 0 025 mmol) in methanol (1 ml) and ethyl acetate (1 ml), 10% palladium catalyst (2 mg) was added Under a hydrogen atmosphere, the reaction mixture was stirred for 5 hours at room temperature and then filtered to remove the catalyst After distilling off the solvent under reduced pressure, the resulting residue was purified by silica gel column chromatography (developing solution = methylene chloride methanol (10 1)) to give the title compound (9 8 mg, 99%) 1 H-NMR (CD3OD) d 1 19 (3H, t, J = 7 5Hz), 2 57 (2H, q, J = 7 5, 7 8Hz), 3 41 -3 47 (1 H, m), 3 64 (1 H, dd, J = 6Hz), 3 73-3 83 (4H, m), 3 95 (2H, s), 5 1 1 (2H, dd, J = 7 8, 12 3Hz), 7 06-7 12 (4H, m), 7 16-7 23 (3H, m) MS (ESI +) 387 [M + 1] + Time of retention of CLAR 1 1 4 minutes < CLAR Condicions > Column YMC-Pack ODS-A 6 0 x 150 mm, 5 μm Mobile phase 20 minutes, gradient of 0 1% TFA / MeCN (5%) + 0 1% TFA / H2O (95%) at 0 1% TFA / MeCN (100%), followed by 5 minute elution under the same conditions (0 1% TFA / MeCN (100%)) Flow rate 1 5 ml / minute Column temperature room temperature Total detection conditions of graphs summed over the entire wavelength range from 230 to 400 nm EXAMPLE 2 1, 1 -Anhydro-1 -C-f 5- (2-benzothiophenyl) methyl-2- (hydroxymethyl) phenyl-β-D-glucopyranose 1) Synthesis of 1, 1-anhydro-1-C- [5- (2-benzot? Ofen? L) h? Drox? Met? L-2- (hydro? Met? L) fen? Ll -2,3,4,6-tetra-O-benzyl-D-qlucopranose Under a stream of nitrogen, to a solution of benzothiophene (51 8 mg, 0 386 mmol) in THF (750 μl) , a hexane solution of n-butyllithium (2 71 M, 130 μL, 0 352 mmol) was added dropwise at -78 ° C and the mixture was stirred for 10 minutes After stirring at room temperature for 30 minutes , the reaction mixture was cooled to -78 ° C, and a solution of 1.1 -anh? dro-1-C- [5-form? -l-2- (hydrox? met? l) phen? ] -2,3,4,6-tetra-O-benzyl-β-D-glucopyranose (207 mg, 0 315 mmol) in THF (450 μl) was added dropwise thereto After stirring at room temperature At room temperature for 1 hour, saturated aqueous ammonium chloride was added and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under high pressure. educted to remove the solvent The resulting residue was purified by silica gel chromatography (developing solution = ethyl acetate n-hexane (1 3)) to give the title compound (266 mg) as a diastereopropy mixture in quantitative yield 1 H-NMR (CDCl 3) d 2 (0 6H, d, J = 3 8Hz), 2 56 (0 4H, d, J = 4 OHz), 3 61 -3 69 (1 H, m), 3 75-3 87 (2H, m), 3 90 (1 H, dd, J = 9 6, 9 6Hz), 4 05-4 18 (3H, m), 4 41 -4 65 (4H, m), 4 84-4 95 (3H, m), 5 21 (2H, s), 6 08 (0 4H, d, J = 3 8Hz), 6 1 1 (0 6H, d, J = 4 OHz), 6 68-6 76 (2H, m), 7 00-7 40 (21 H, m), 7 40-7 70 (5H, m) 2) Synthesis of 1, 1 -anh? Dro-1-C- [5- (2-benzot? Ofen? L) met? L-2- (hydro? Met? L) phen? L-2, 3 , 4,6-tetra-O-benzl-β-D-qlucopranyose Under a stream of nitrogen, to a solution of 1.1 -anhydr-1-C- [5- (2-benzot? ofen? l) -h? drox? met? l-2- (hydrox? met? l) phen? l] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose (249 mg, 0 315 mmol) in acetonite (3 ml), tpethylsilane (60 μl, 0 376 mmol) and boron trifluoride-diethyl ether complex (42 μl, 0.331 mmol) were added at -40 ° C and the The mixture was stirred at the same temperature for 2 hours. After the addition of saturated aqueous potassium carbonate, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate. , and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel chromatography (developing solution = ethyl acetate n-hexane (1 4)) to give the title compound. or (103 mg, 42%) as a diastherometric mixture 1 H-NMR (CDCl 3) d 366 (1H, dd, J = 18, 11 1Hz), 380 (1H, dd, J = 37, 112Hz), 384 (1H, dd, J = 95, 95Hz), 388 (1H , d, J = 95Hz), 405-415 (3H, m), 421 (1H, d, J = 160Hz), 425 (1H, d, J = 160Hz), 446 (1H, d, J = 122Hz), 449 (1H, d, J = 107Hz), 458 (1H, d, J = 122Hz), 461 (1H, d, J = 107Hz), 483-495 (3H, m), 518 (1H, d, J = 127Hz), 519 (1H, d, J = 125Hz), 674 (1H, dd, J = 82, 17Hz), 693 (1H, s), 706-736 (23H, m), 750 (1H, dd, J = 72, 14Hz), 761 (1H, d, J = 79Hz) 3) Synthesis of 1,1-anhydro-1-C- [5- (2-benzot? Ofen? L) met? L-2- (hydro? Met? L) phen? P-b-D -qlucopranose Under a stream of nitrogen, to a solution of 1,1-anhydro-1-C- [5- (2-benzot? ofen? l) met? l-2- (hydrox? met) ?) fen? l] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose (307 mg, 00396 mmol) and pentamethylbenzene (606 mg, 0409 mmol) in dichloromethane (2 ml. ), a solution in 10 M dichloromethane of boron tpchloride (400 μl, 0400 mmol) was added at -78 ° C and the mixture was stirred at the same temperature for 1 hour. After the addition of methanol, the reaction mixture was warmed to room temperature and evaporated under reduced pressure to remove the solvent The resulting residue was purified by thin layer chromatography (developing solution = methanol dichloromethane (1:10)) to give the title compound (104 mg, 638%) 1H -NRM (CD3OD) d 344 (1H, ddd, J = 90, 53, 35Hz), 365 (1H, dd, J = 116, 53Hz), 372-386 (4H, m), 427 (2H, s), 510 (1H, d, J = 127Hz), 14 (1 H, d, J = 12 7Hz), 7 07 (1 H, s), 7 18-7 37 (5H, m), 7 66 (1 H, dd, J = 1 5, 7 OHz), 7 72 (1 H, d, J = 8 1 Hz) EM (ESI +) 414 [M] + Retention time of CLAR 12 3 minutes < CLAR Condicions > Column YMC-Pack ODS-A 6 0 x 150 mm, 5 μm Mobile phase 20 minutes, gradient of 0 1% of TFAVMeCN (5%) + 0 1% TFA / H2O (95%) at 0 1% TFA / MeCN (100%), followed by 5 minute elution under the same conditions (0 1% TFA / MeCN (100%)) Flow rate 1 5 ml / minute Column temperature ambient temperature Total detection conditions of graphs summed over the entire wavelength range from 230 to 400 nm EXAMPLE 3 1,1-Anhydro-1-C-r5- (4-methoxyphenyl) methyl-2- (hydroxymethyl) phenin-β-D-glucopyranose 1) Synthesis of 1, 1 -anh? Dro-1-C- [5- (4-methox? Phen? L) h? Drox? Met? L-2- (hydro? Met? L) phen? Ll -2,3,4,6-tetra-O-benzyl-β-D-qlucopyranose Under a stream of nitrogen, to a solution of 1, 1 -anh? Dro-1 -C- [5-form L-2- (hydroxymethyl) phen? l] -2,3,4,6-tetra-O-benzyl-β-D-glucopyrane (2 01 g, 3 06 mmol) ) in diethyl ether (24 ml), a THF solution of 4-methoxyphenemagnes? bromide (0 5 M, 12 24 ml, 6 12 mmol) at 0 ° C and the mixture was stirred for 2 hours and 30 minutes at room temperature After addition of water, the The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by flash column chromatography. silica gel (developing solution = ethyl acetate n-hexane (1 4)) to give the title compound (2 15 g, 92%) 1 H-NMR (CDCl 3) d 3 63 (1 H, d, J = 9 9Hz), 3 69 (3H, s), 3 78-3 90 (3H, m), 4 08-4 1 1 (2H, m), 4 43-4 64 (4H, m), 4 89 (3H , d, J = 10 2Hz), 5 17 (2H, s), 5 81 (1 H, s), 6 67 (2H, m), 7 06-7 48 (25H, m) 2) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-methox? Phen?) Met? L-2- (hydro? Met? L) fen? Ll-2,3 , 4,6-tetra-O-benzyl-β-D-qlucopyranose Under a stream of nitrogen, to a solution of 1.1 -anh? Dro-1-C- [5- (4-methoxy? fen? l) h? drox? met? l-2- (hydrox? met? l) phen? l] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose ( 270 mg, 0.353 mmol) in methylene chloride (2.7 ml), t-phenylsilane (281 μL, 1764 mmol) and boron-trifluoride diethyl ether complex (47 μL, 0.37 mmol) were added at -40 ° C. and the mixture was stirred at the same temperature for 15 minutes. After the addition of water, the reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1:10)) to give the title compound (260 mg, 90%) 1 H-NMR (CDCl 3) d 3 63 (1 H, d, J = 9 3Hz), 3 69 (3H, s), 3 77-3 81 (1 H, dd, J = 3 9, 3 6Hz), 3 83 (1 H, s), 3 86 (1 H, s), 3 92 (2 H, s), 3 99 (1 H, d, J = 10 8Hz), 4 06-4 14 (2H, m), 4 47 (2H, d, J = 12Hz), 4 56 (1 H, s), 4 61 (2H, d, J = 12 3Hz), 4 84 (1H, d, J = 3Hz), 4 89 (2H, d, J = 4 8Hz), 5 16 (2H, dd, J = 12 3, 1 Hz), 6 60-6 70 (4H, m), 6 98 (2H, d, J = 6 3Hz), 7 07-7 31 (21 H, m) 3) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-methox? Phen?) Met? L-2- (hydro? Met? L) phen? Ll-b-D -glucopyridose To a solution of 1, 1 -anh? dro-1-C- [5- (4-methox? phen?) met? l-2- (hydrox? met? l) phen? l ] -2,3,4,6-tetra-O-benzyl-β-D-glucopyranose (280 mg, 0.381 mmol) in methanol (1 ml) and ethyl acetate (1 ml) was added 10% palladium catalyst (28.7 mg) and 2N HCl (15 2 μl) was added further. Under a hydrogen atmosphere, the reaction mixture was stirred for 45 minutes at room temperature and then filtered to remove the catalyst. Distillation of the solvent under reduced pressure, the resulting residue was purified by silica gel column chromatography (developing solution = methylene chloride methanol (10 1)) to give the title compound (14mg, 98%) 1H- NMR (CD3OD) d 3 36-3 42 (1 H, m), 3 60 (1 H, dd, J = 6 Hz), 3 70 (3 H, s), 3 71 -3 79 (4 H, m), 3 88 (2H, s), 5 02 (2H, dd, J = 12 3, 7 8Hz), 6 74-6 78 (2H, m), 6 79-7 08 (2H, m), 7 12-7 18 (3H, m) EM (ESf) 388 [M] + Retention time of CLAR 9 62 minutes < CLAR Condicions > Column YMC-Pack ODS-A 6 0 x 150 mm, 5 μm Mobile phase 20 minutes, gradient of 0 1% TFA / MeCN (5%) + 0 1% TFA / H2O (95%) at 0 1% TFA / MeCN (100%), followed by 5 minute elution under the same conditions (0 1% TFA / MeCN (100%)) Flow rate 1 5 ml / minute Column temperature room temperature Total detection conditions graphs added over the entire wavelength range from 230 to 400 nm EXAMPLE 4 1, 1 -Anhydro-1 -C-r5- (4-isopropylphenyl) methyl-2- (hydroxymethyl) phenin-β-D-glucopyranose 1) Synthesis of 1, 1-anhydro-1-C- [5- (4-? Soprop? Lfen? L) h? Drox? Met? L-2- (hydro? Met?) Fen? ll-2,3,4,6-tetra-O-benzyl-β-D-qlucopranose Under a stream of nitrogen, a solution of 4-bromoisopropylbenzene (27 20 g, 136 62 mmol) in THF (242 ml) was cooled to -78 ° C and a hexane solution of n-butylthio (2 67 M, 54 37 ml) was added dropwise thereto The reaction mixture was stirred thereto temperature for 1 5 hours A solution of 1.1 -anh? dro-1-C- [5-form? l-2- (hydrox? met? l) phen? l] -2,3,4,6 -tetra-O-benzyl-β-D-glucopyranose (56.08 g, 85 39 mmol) in THF (232 ml) was added dropwise and the mixture was stirred at -78 ° C for 1 5 hours Saturated aqueous ammonium chloride was added to stop the reaction. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1-3)) to give the title compound (5778 g, 87%) as a 1H diastereomeric mixture. -RMN (CDCI3) d 1 14 (6H, d, J = 6 9Hz), 2 08 (0 6H, d, J = 3 3Hz), 2 15 (0 4H, d, J = 3 6Hz), 2 75- 2 81 (1 H, m), 3 63-3 67 (1 H, m), 3 76-4 15 (6H, m), 4 42-4 64 (4H, m), 4 84-4 94 (3H , m), 5 12-5 22 (2H, m), 5 80-5 84 (1 H, m), 6 64-6 68 (2H, s), 7 02-7 49 (25H, m) 2) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-? Soprop? Lfen? L) met? L-2- (hydro? Met? L) fen? Ll-2, 3,4,6-tetra-O-benc? L-ß-D-qlucop? Canosa Under a stream of nitrogen, at 1, 1 -anh? Dro-1-C- [5- (4-? Soprop? Lfen? L ) h? drox? met? l-2- (hydrox? met? l) phen? l] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose (2 186 g) 2 81 mmol) in dichloromethane (28 ml), tpethylsilane (2 24 ml, 14.02 mmol) and boron trifluoride-diethyl ether complex (0 38 ml, 3 00 mmol) were added at -40 ° C and the mixture was added. he stirred to it temperature for 1 5 hours After the addition of saturated aqueous potassium carbonate, the reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 5)) to give the title compound (1 81 g, 85%) 1 H-NMR (CDCl 3) d, 1 16 (6H, dd, J = 6 9, 0 8Hz), 2 77-2 81 (1 H, m), 3 65 (1 H, dd, J = 1 1 0, 1 6Hz), 3 78-3 87 (3H, m), 3 95-4 01 (3H, m), 4 06-4 15 (2H, m), 4 45 (2H, d, J = 12 1 Hz) , 4 56-4 63 (2H, m), 4 64 (1 H, s), 4 85- 4 94 (3H, m), 5 15 (2H, dd, J = 17 6, 12 4Hz), 6 68 -6 71 (2H, m), 7 00-7 31 (25H, m) 3) Synthesis of 1, 1 -anh? Dro-1-C-f5- (4-? Soprop? Lfen? L) -met? L-2- (hydro? Met? L) fen? Ll-b- D-qlucopranose To a solution of 1, 1 -anh? Dro-1-C- [5- (4-? Soprop? Lfen? L) met? L-2- (hydrox? Met? L) phen ?] -2,3,4,6-tetra-O-benzyl-β-D-glucopyranose (1 78 g, 2 34 mmol) in methanol (11 ml) and ethyl acetate (11 ml), 10% palladium catalyst (0.22 g) was added. Under a hydrogen atmosphere, the reaction mixture was stirred for 1 hour at room temperature and then filtered to remove the catalyst After distilling off the solvent under reduced pressure , the resulting residue was purified by silica gel column chromatography (developing solution = methylene chloride methanol (10 1)) to give the title compound (0 75 g, 80%) 1 H-NMR (CD 3 OD) d 1 21 (6 H, d, J = 6 9 Hz), 2 82-2 86 (1 H, m), 3 43-3 47 (1 H, m), 3 64 (1 H, dd, J = 12 1, 5 8Hz), 3 74-3 81 (4H, m), 3 95 (2H, s), 5 1 1 (2H, dd, J = 19 5, 12 4Hz), 7 1 1 (4H, s), 7 16-7 22 (3H, m) EM (ESI +) 401 [M + 1] + Retention time of CLAR 12 1 minutes < CLAR Condicions > Column YMC-Pack ODS-A 6 0 x 150 mm, 5 μm Mobile phase 20 minutes, gradient of 0 1% TFA / MeCN (5%) + 0 1% TFA / H2O (95%) at 0 1% TFA / MeCN (100%), followed by 5 minute elution under the same conditions (0 1% TFA / MeCN (100%)) Flow rate 1 5 ml / minute Column temperature room temperature Total detection conditions graphs added over the entire wavelength range from 230 to 400 nm EXAMPLE 5 l.l-Anhydro-l -C-fS ^ -cyclopropylpheniDmethyl ^ -hydroxymethiDfenin-β-D-glucopyranose 1) Synthesis of 1, 1 -anh? Dro-1 -C-f5- (4-c? Cloprop? Lfen? L) h? Drox? Met? L- 2- (hydro? Met?) Fen? ll-2,3,4,6-tetra-O-benc? l-β-D-qlucop? canosa Under a stream of nitrogen, to a suspension of magnesium (0 27 g, 1 1 1 mmoles) and 4- bromo-clopropylbenzene (2 00 g, 10 15 mmol) in ether (21 ml), 1,2-d-bromoethane (0 014 ml, 0 16 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour. 5 hours and then cooled to 0 ° C, followed by the dropwise addition of a solution of 1.1 -anhydr-1-C- [5-formyl-2- (hydrox? Met? l) phenol] -2,3,4,6-tetra-O-benzyl-β-D-glucopyranose (5 10 g, 7 77 mmol) in ether (21 ml) After stirring at 0 ° C for 1 hour, saturated aqueous ammonium chloride was added to stop the reaction. The reaction mixture was extracted twice with ether. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then evaporated under pressure. reduced to remove the solvent The resulting residue was purified by silica gel chromatography (developing solution = n-hexane acetone (3 1)) to give the title compound (5 18 g, 86%) 1 H-NMR (CDCl 3) d 0 55-0 59 (2H, m), 0 86-0 92 (2H, m), 1 75-1 82 (1 H, m), 2 12 (1 H, d, J = 3 6Hz), 3 62-4 15 (7H , m), 4 43-4 64 (4H, m), 4 86-4 90 (3H, m), 5 12-5 21 (2H, m), 5 78-5 88 (1 H, m), 6 65-6 69 (1 H, m), 6 85-7 41 (26H, m) 2) Synthesis of 1, 1 -anh? Dro-1 -C-f5- (4-c? Cloprop? Lfen? L) met? L-2- (h? Drox? Met? L) phen? N-2, 3,4,6-tetra-O-benzyl-β-D-qlucopranose Under a stream of nitrogen, at 1, 1 -anh? Dro-1-C- [5- (4-c? Cloprop? lfen? l) h? drox? met? l-2- (hydrox? met? l) fen? l] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose ( 5 16 g, 6 66 mmol) in dichloromethane (67 ml), tpethylsilane (5 30 ml, 33 18 mmol) and boron trifluoride-diethyl ether complex (0 91 ml, 7 18 mmol) were added at -40 ° C. and the mixture was stirred at the same temperature for 15 hours. After the addition of saturated aqueous potassium carbonate, the reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over sulfate. of anhydrous magnesium, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (14)) to give the titer (4 27 g, 85%) 1 H-NMR (CDCl 3) d 0 56-0 58 (2 H, m), 0 86-0 90 (2 H, m), 1 74-1 84 (1 H, m) , 3 63-3 67 (1 H, m), 3 77-3 86 (3H, m), 3 94 (2H, s), 3 99 (1 H, d, J = 10 4Hz), 4 07-4 14 (2H, m), 4 45 (2H, d, J = 12 1 Hz), 4 56-4 63 (2H, m), 4 85-4 90 (3H, m), 5 1 1-5 20 ( 2H, m), 6 68-6 71 (2H, m), 6 83-6 86 (2H, m), 6 97 (2H, d, J = 8 2Hz), 7 09-7 31 (21H, m ) 3) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-c? Cloprop? Lfen? L) met? L-2- (hydro? Met? L) fen? Ll-b -D-Glucopyranose Under a stream of nitrogen, to a solution of 1.1 -anh? Dro-1-C- [5- (4-c? Cloprop? Lfen? L) met? L-2- (h ? drox? met?) fen? l] -2,3,4,6-tetra-O-benz? -l-D-glucopyranose (2 55 g, 36 mmoles) and pentamethylbenzene (4 99 g, 33 66 mmoles) in dichloromethane (185 ml), a solution in 1 0 M dichloromethane boron tpchloride (33 26 ml, 33.26 mmol) was added at -78 ° C and the mixture was stirred at the same temperature for 2 hours. After the addition of methanol (185 ml), the reaction mixture was warmed to room temperature and evaporated under reduced pressure. to remove the solvent The resulting residue was purified by thin layer chromatography (developing solution = methanol dichloromethane (110)) to give the title compound (0 67 g, 50%) 1 H-NMR (CD3OD) d 0 59- 0 64 (2H, m), 0 87-0 94 (2H, m), 1 82-1 87 (1 H, m), 3 40-3 47 (1 H, m), 3 61 (1 H, dd , J = 12 1, 5 8Hz), 3 74-3 83 (4H, m), 3 94 (2H, s), 5 09 (2H, dd, J = 20 3, 12 4Hz), 6 94-6 97 (2H, m), 7 05-7 08 (2H, m), 7 19 (3H, m) EM (ESI +) 398 [M] + Retention time of CLAR 1 1 4 minutes <; CLAR Condicions > Column YMC-Pack ODS-A 6 0 x 150 mm, 5 μm Mobile phase 20 minutes, gradient of 0 1% TFA / MeCN (5%) + 0 1% TFA / H2O (95%) at 0 1% TFA / MeCN (100%), followed by circumvention of 5 minutes under the same conditions (0 1% TFA / MeCN (100%)) Flow rate 1 5 ml / minute Column temperature room temperature Total detection conditions of graphs summed over the full wavelength range of 230 to 400 nm EXAMPLE 6 1, 1 -Anhydro-1 -C-r5- (4-n-propylphenyl) methyl-2- (hydroxymethyl) phenyl] -β-D-glucopyranose 1, 1-anhydr-1 -C- (5- (4-c? Cloprop? Lfen? L) -met? L-2- (hydro? Met? L) phen? L] -2.3 , 4,6-tetra-O-benzyl-β-D-glucopyranose obtained in example 5 (1 68 g, 217 mmol) was dissolved in methanol (10 ml) and ethyl acetate (10 ml) To this solution, 10% pallate catalyst (0 21 g) was added. Under a hydrogen atmosphere, the reaction mixture was stirred for 1 5 hours at room temperature and then filtered to remove the catalyst. After distilling the solvent under reduced pressure, the resulting residue was purified by silica gel column chromatography (developing solution = methylene chloride methanol (10 1) to give the title compound (0 65 g, 73%) 1 H-NMR (CD 3 OD) d 0 92 (3H, t, J = 7 4Hz), 1 57-1 64 (2H, m), 2 50-2 55 (2H, m), 3 43-3 49 (1 H, m), 3 65 ( 1 H, dd, J = 1 1 8, 5 5Hz), 3 75-3 85 (4H, m), 3 95 (2H, s), 5 09 (2H, dd, J = 19 2, 12 4Hz), 7 04-7 22 (7H, m) MS (ESf) 401 [M + 1] + Retention time of CLAR 12 3 minutes < CLAR Condicions > Column YMC-Pack ODS-A 6 0 x 150 mm, 5 μm Mobile phase 20 minutes, gradient of 0 1% of TFA / MeCN (5%) + 0 1% TFA / H2O (95%) at 0 1% TFA / MeCN (100%), followed by 5 minute elution under the same conditions (0 1% TFA / MeCN (100%)) Flow rate 1 5 ml / minute Column temperature ambient temperature Total detection conditions of graphs summed over the entire wavelength range from 230 to 400 nm EXAMPLE 7 1.1 -Anhydro-1-C- [5- (4-ethylphenyloxy) -2- (hydroxymethyl) phenan-β-D-9-glucopyranose 1) Synthesis of 2-bromo-4- (et? Lphenox) -benzoic acid methyl ester To a solution of 2-bromo-4-fluoro-benzoic acid methyl ester (488 mg, 2 09 mmol) in anhydrous DMF (15 ml), 4-et? Lphenol (256 mg, 2.09 mmol) and potassium carbonate (289 mg, 2.09 mmol) were added at room temperature, followed by stirring under a nitrogen atmosphere for 16 hours at 160 ° C. C The reaction mixture was cooled and, after the addition of saturated aqueous ammonium chloride, extracted with ethyl acetate The organic layer was washed with saturated aqueous sodium chloride and dried over sodium sulfate. After filtration, the solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (developing solution = sodium acetate). ethyl n-hexane (1 20)) to give the title compound (455 mg, 65%) 1 H-NMR (CDCl 3) d. 1.26 (3H, t, J = 7.6Hz), 2.67 (2H, q, J = 7.6Hz), 3.90 (3H, s), 6 88-6 93 (1 H, m), 6 94-7.01 (2H, m), 7.19-7.26 (3H, m), 7 83 (1 H, d, J = 8 7Hz) 2) Synthesis of [2-bromo-4- (4-ethylphenoxy) phenylmethanol Under a stream of nitrogen, to a solution of 2-bromo-4- (et? Lphenox) -benzoic acid methyl ester (90 mg 0.269 mmole) in anhydrous toluene (2 ml), a toluene solution of DIBAL (1M, 0.537 ml, 0 537 mmole) was added dropwise at -78 ° C. The reaction mixture was stirred at -78 ° C for 1.5 hours and at room temperature for 1.5 hours. The reaction mixture was again cooled to -78 ° C, followed by the addition of 1 N hydrochloric acid (0 2 ml) and ether ( 3.5 ml) The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over sodium sulfate. After filtration, the solvent was distilled under reduced pressure and the resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 5)) to give the title compound (78 mg , 94%) 1 H-NMR (CDCl 3) d 1 25 (3 H, t, J = 7 6 Hz), 2.65 (2 H, q, J = 7 6 Hz), 4 71 (2H, s), 6 91 -6 97 (3H, m), 7 15-7 21 (3H, m), 7 39 (1 H, d, J = 8 4Hz) 3) Synthesis of (2-tpt? Lox? Met? L) -5- (4-et? Lfenox?) - phenol bromide Under a stream of nitrogen, to a solution of [2-bromo-4- (4-et? lfenox?) phen? l] methanol (493 mg, 1 61 mmol) in a mixture of anhydrous DMF (5 ml) and methylene chloride (5 ml. ), thptyl chloride (492 mg, 1 77 mmol), tetylamine (0 247 ml, 1 77 mmol) and 4-dimethylaminopip- tam (50 mg) were added. The reaction mixture was stirred at room temperature for 12 hours after the addition. of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over sodium sulfate. After filtration, the solvent was distilled off under reduced pressure and the resulting residue was purified by chromatography. on a column of silica gel (developing solution = ethyl acetate n-hexane (1 9)) to give the title compound (880 mg, 99%) 1 H-NMR (CDCl 3) d 1 25 (3H, t, J = 7 6Hz), 2 65 (2H, q, J = 7 6Hz), 4 19 (2H, s), 6 91 -7 34 (15H, m), 7 49-7 53 (6H, m), 7 64 -7 68 (1 H, m) 4) Synthesis of 3,4,5-tps-benz? Lox? -6-benz? Lox? Met? L-2- [5- (4-et? Lfenox?) - 2-tr? T? Lox? Met ? lfen? lltetrah? drop? ran-2-ol Under a stream of nitrogen, to a solution of bromide (2-tr? t? lox? met? l) -5- (4-et? lfenox?) fen? (766 mg, 1.39 mmol) in anhydrous THF (15 ml), a hexane solution of n-butyllithium (1 6 M, 092 ml, 1 47 mmol) was added dropwise at -78X and the mixture was stirred for 15 minutes To this solution was added dropwise a solution of 3,4,5-tr? sbenc? lox? -6- (benz? lox? met? ) tetrah? drop? ran-2-one (751 mg, 1 39 mmol) in anhydrous THF (15 ml) at -78 ° C and the resulting solution was stirred at the same temperature for 10 minutes after the addition of chloride of saturated aqueous ammonium, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (17)) to give the title compound (615 mg, 43%) 1 H-NMR (CDCl 3) d 1 22 (3H, t, J = 7 6Hz), 2 62 (2H, q, J = 7 6Hz), 3 30-3 59 (4H, m), 3 80-4 05 (3H, m), 4 25-4 39. { 5H, m), 4 46-4 62 (2H, m), 4 72-4 85 (3H, m), 6 80-7 59 (42H, m) ) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-et? Lfenox?) - 2- (hydrox? Met? L) -fen? Ll-2,3,4, 6-tetra-O-benzyl-β-D-qlucopyranose Under a stream of nitrogen, to a solution of 3,4,5-tr? S-benzyl? -6-benzyl? Met? l-2- [5- (4-et? lfenox?) - 2-tpt? lox? met? lfen? l] tetrah? drop? ran-2-ol (547 mg, 054 mmol) in methylene chloride ( 10 ml), t-phenylsilane (0 095 ml, 0 60 mmol) and TFA (0 046 ml, 0 60 mmol) were added at 0 ° C, followed by stirring at room temperature for 2 hours after the addition of aqueous potassium carbonate. saturated, the reaction mixture is extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography ( developing solution = ethyl acetate n-hexane (14)) to give the title compound (405 mg, 99%) 1 H-NMR (CDCl 3) d 1 22 (3H, t, J = 7 6Hz), 2 62 (2H, q, J = 7 6Hz), 3 59-3 87 (4H, m), 4 04-4 21 (3H, m), 4 41 -4 68 (4H, m), 4 81 -4 95 ( 3H, m), 5 1 1 -5 24 (2H, m), 6 77-6 91 (4H, m), 6 95 (1 H, d, J = 1 9Hz), 7 01 -7 36 (22H, m) MS (ESI +) 772 [M + Na] + 6) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-et? Lfenox?) - 2- (hydrox? Met? L) phen? N-? -D-qlucop? Ranosa To a solution of 1.1 -anh? Dro-1-C- [5- (4-et? Lpheox?) -2- (hydro? Met? L) phen? L] -2.3.4, 6-tetra-O-benzyl-β-D-glucopyranose (429 mg, 0.57 mmol) in a mixture of ethyl acetate (12 ml) and methanol (12 ml), 10% of the catalyst was added. palladium (400 mg) Under a hydrogen atmosphere, the reaction mixture was stirred for 12 hours at room temperature and then filtered to remove the catalyst. After distilling off the solvent under reduced pressure, the resulting residue was purified by column chromatography. silica gel (developing solution = methylene chloride methanol (10 1)) to give the title compound (195 mg, 88%) 1 H-NMR (CD 3 OD) d 1 23 (3 H, t, J = 7 6 Hz), 2 63 (2 H, q, J = 7 6 Hz), 40-3 46 (1 H, m), 3 63-3 85 ( 5H, m), 5 10 (2H, m), 6 87-7 03 (4H, m), 7 14-7 28 (3H, m) MS (ESI +) 41 1 [M + Na] + EXAMPLE 8 1.1-Anhydro-1 -C-r5- (4-ethylphenyl) methyl-2- (2-hydroxyethyl) thiophen-3-in-ß-D-glucopyranose 1) Synthesis of (4-bromo-t? Ofen-2? L) - (4-et? L-phen? L) methanol Under a stream of nitrogen, to a solution of 4-bromo-2-thiophenecarboxaldehyde (10). 0 g, 52 3 mmol) in anhydrous THF (100 ml), a hexane solution of n-butyl-thio (1 6 M, 34 35 ml, 55 0 mmol) was added dropwise at -78 ° C for 5 hours. minutes After stirring at the same temperature for 10 minutes, a solution of 1-bromo-4-et? -benzene (10.2 g, 55.0 mmol) in THF (50 ml) was added dropwise. The reaction mixture was stirred at -78 ° C for 2 hours andAfter the addition of saturated aqueous ammonium chloride, it was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1:10)) to give the title compound (7 1 g, 45%) 1 H-NMR (CDCl 3) d 1 24 (3 H, t, J = 7 5 Hz), 2 42 (1 H, s), 2 65 (2 H, q, J = 7 5 Hz), 5 93 (1 H, s) , 6 76 (1 H, s), 7 14 (1 H, s), 7 20 (2 H, d, J = 8 1 Hz), 7 32 (2 H, d, J = 8 1 Hz) 2) Synthesis of 4-bromo-2- (4-et? L-phen? L) -met? Lt? Ofeno Under a stream of nitrogen, to a solution of (4-bromo-t? Ofen-2? ) - (4-et? L-phen? L) -methanol (7 10 g, 23 9 mmol) in methylene chloride (70 ml), tpethylsilane (4 6 ml, 28 7 mmoles) and tetrafluoride complex were added. boron-diethyl ether (3 33 ml, 26 3 mmol) at 0 ° C, followed by stirring at room temperature for 2 hours After the addition of 50% methanol-water (1 ml), the reaction mixture was extracted with methylene chloride The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (silica gel solution). revealed = ethyl acetate n-hexane (150)) to give the title compound (3 4 g, 51%) 1 H-NMR (CDCl 3) d 1 23 (3 H, t, J = 7 5 Hz), 2 63 ( 2H, q, J = 7 5Hz), 4 06 (2H, s), 6 70 (1 H, s), 7 02 (1 H, s), 7 14 (4H, s) 3) Synthesis of 2- [3-bromo-5 - ((4-et? Lfen? L) met? L) t? Ofen-2? -methanol Under a stream of nitrogen, to 4-bromo-2 - (( 4-et? Lfen? L) met? L) t? Ofeno (2 80 g 10 0 mmol) in anhydrous THF (40 ml), LDA (2.0 M, 50 ml, 10 ml) was added dropwise. ) at -78 ° C for 5 minutes After the reaction mixture was stirred at 0 ° C for 30 minutes, a THF solution of ethylene oxide (10 ml) was added dropwise at -78 ° C. The reaction mixture was warmed to room temperature and stirred for 3 hours After the addition of water, the reaction mixture was extracted with ether. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 9)) to give the title compound (2 55 g, 78%) 1 H-NMR (CDCl 3) d 1 23 (3H, t, J = 7 5Hz), 1 60 (1 H, s), 2 63 (2H, q, J = 7 5Hz), 2 96 (2H, t, J = 6 3Hz), 3 80 ( 2H, t, J = 6 3Hz), 4 00 (2H, s), 6 62 (1 H, s), 7 14 (4H, s) 4) Synthesis of 3-bromo-5- (4-et? Lfen? L) -met? L-2- (2-tr? T? Lox? Et? L) t? Ofeno Under a stream of nitrogen, at a solution of 2- [3-bromo-5- ((4-et? lfen? l) met? l) t? ofen-2? l] -ethanol (2 55 g, 7 84 mmol) in a mixture of DMF anhydrous (15 ml) and methylene chloride (15 ml), was added thptyl chloride (3 29 g, 1 l 8 mmol) To this solution, thnecylamine (1 64 ml, 1 l 8 mmol) and 4-d were added. ? met? lam? nop? r? d? na (77 mg, 0 63 mmol) at 0 ° C The reaction mixture was stirred at 40 ° C for 4 hours After the addition of water, the reaction mixture was extracted with methylene chloride The organic layer was washed with saturated aqueous sodium chloride and dried over sodium sulfate. After filtration, the solvent was distilled under reduced pressure and the residue The resulting product was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 20)) to give the title compound (3 60 g, 81%) 1 H-NMR (CDCl 3) d 1 (3H, t, J = 7 5Hz), 2 62 (2H, q, J = 7 5Hz), 2 96 (2H, t, J = 6 3Hz), 3 26 (2H, t, J = 6 3Hz), 4 00 (2H, s), 6 60 (1 H, s), 7 12 (4H, s), 7 12-7 27 (9H, m), 7 37-7 40 (6H, m) ) Synthesis of 3,4,5-tps-benc? Lox? -6-benz? Lox? Met? L-2- [5- (4-et? Lfen? L) met? L-2- (2- tpt? lox? et? l) t? ofen-3-? n-tetrah? drop? ran-2-ol Under a stream of nitrogen, to a solution of 3-bromo-5- (4-et? lfen? l ) methanol) -2- (2-tpt? lox? et? l) t? ofeno (1 45 g, 2 55 mmol) in anhydrous THF (40 ml), a hexane solution of n-butylthio ( 1 6 M, 76 ml, 2 81 mmol) was added dropwise at -78 ° C and the mixture was stirred for 15 minutes. To this solution was added dropwise a solution of 3,4,5-tpsbenc? Lox ? -6- (benz? Lox? Met? L) tetrah? Drop? Ran-2-one (1 50 g, 2.81 mmol) in anhydrous THF (10 ml) at -78 ° C and the resulting solution was stirred at the same temperature for 10 minutes After the addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent. The resulting residue was purified by chromatography on silica gel column (developing solution = ethyl acetate n-hexane (1 20)) to give the title compound (1 70 g, 65%) 1 H-NMR (CDCl 3) d 1 22 (3 H, t, J = 4 5 Hz), 2 56 (1 H, d, J = 9 3 Hz), 2 62 (2H, q, J = 4 5Hz), 3 26-3 31. { 2H, m), 3 39 (1 H, d, J = 6 OHz), 3 47 (1 H, d, J = 5 4Hz), 3 75-4 08 (8H, m), 4 48 (2H, t , J = 7 5Hz), 4 60 (1 H, d, J = 7 2Hz), 4 66 (1 H, d, J = 6 6Hz), 4 87 (2H, q, J = 3 3Hz), 4 95 (1 H, d, J = 6 6Hz), 5 25 (1 H, s), 6 84 (1 H, s), 7 02-7 31 (39H, m) MS (ESF) 1049 [M + Na] + 6) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-et? L-phen? L) -met? L-2- (2-h? Drox? Et? L) -t ? ofen-3-? l1-2,3,4,6-tetra-O-benc? l-ß-D-qlucop? ranosa Under a stream of nitrogen, to a solution of 3,4,5-tr? s? -benc? lox? -6-benz? lox? met? l-2- [5- (4-et? l-benc? l) -2- (2-tpt? lox? -et? l) -t? ofen-3-? lj-tetrah? drop? 2-ol (1 70 g, 1 68 mmol) in methylene chloride (60 ml), tpethylsilane (0 30 ml, 1.85 mmol) and ether complex were added. diethyl alcohol (0.234 ml, 1.85 mmol) at 0 ° C, followed by stirring at room temperature for 2 hours. After the addition of saturated aqueous potassium carbonate, the reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvent The resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (1 9)) to give the compound of titer (1 14 g, 84%) 1 H-NMR (CDCl 3) d 1 19 (3 H, t, J = 4 5 Hz), 2 56-2 59 (3 H, m), 3 02-3 09 (1 H, m) 3 69 (1 H, d, J = 6 OHz), 3 75-3 81 (3H, m), 3 95-4 12 (6H, m), 4 18 (1 H, d, J = 7 3Hz), 4 50 (2H, dd, J = 6 9, 9 0 Hz), 4 60 (2H, m), 4 86 (2H, d, J = 5 4Hz), 4 93 (1 H, d, J = 6 6Hz), 6 62 (1 H, s), 6 88 (2H, d, J = 3 9Hz), 7 03 (2H, d, J = 4 8Hz), 7 08 (2H, d, J = 4 8Hz), 7 16-7 33 (18H, m) MS (ESI +) 789 [M + Na] + 7) Synthesis of 1, 1 -anh? Dro-1 -C - [(4-et? L-phen? L) -met? L-2- (2-h? Drox? Et? Dt? Ofen-3-- ? ll-ß-D-qlucop? ranosa Under a stream of nitrogen, to a solution of 1, 1 -anh? dro-1-C- [5- (4-et? lfen? l) met? l-2- (2-H? Drox? Et? L) t? Ofen-3-? L] -2,3,4,6-tetra-O-benc? L-β-D-glucopyranose (1 14 g, 1 46 mmol) ) in anhydrous methylene chloride (50 ml), pentamethylbenzene (3 25 g, 21 9 mmol) was added at -78 ° C boron tetrachloride (14 6 ml, 14 6 mmol) was added further, followed by stirring at -78 ° C for 2 hours After the addition of methanol, the solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (developing solution = methylene chloride methanol (20 1)) to give the compound title (350 mg, 59%) 1 H-NMR (CD 3 OD) d 1 20 (3 H, t, J = 7 5 Hz), 2 52-2 64 (3 H, m), 2 93-3 03 (1 H, m), 3 34-3 37 (1 H, m), 3 61 -3 83 (5H, m), 3 96-4 05 (4H, m), 6 67 (1 H, s), 7 09-7 15 (4H, m) MS (ESI +) 407 [M + 1] + EXAMPLE 9 1, 1-Anhydro-1 -C-f5- (4-biphenyl) -methyl-2-hydroxymethinfenin-β-D-glucopyranose 1) Synthesis of 1, 1 -anh? Dro-1 -C-f2,5-b? S- (hydrox? Met? L) fen? Ll -β-D-qlucopyranose 1.1, -Anh? 1 -C- [2,5-b? S- (hydrox? Met? L) phen? L] -2,3,4,6-tetra-O-benzyl-β-D-glucopyranose synthesized in the example 1 (0 59 g, 0 90 mmol) and pentamethylbenzene (1 33 g, 8 95 mmol) were dissolved in dichloromethane (48 ml) To this solution, under a stream of nitrogen, a solution in 1 0 M dichloromethane of boron t-chloride (8 95 ml, 895 mmol) was added at -78 ° C and the mixture was stirred at the same temperature for 2 hours. After the addition of methanol (48 ml), the reaction mixture was warmed to room temperature and evaporated under reduced pressure to remove the solvent The resulting residue was purified by thin layer chromatography (developing solution = methanol dichloromethane (1 6)) to give the title compound (018 g, 67%) 1 H-NMR (CD3OD) d 3 47-3 50 (1 H, m), 3 63-3 69 (1 H, m), 3 75-3 85 (4H, m), 4 63 (2H, s), 5 13 (2H, dd , J = 12 6, 19 5Hz), 7 23-7 37 (3H, m ) MS (ESI +) 299 [M + 1] + 2) Synthesis of 1, 1 -anh? Dro-1-C- [5-chloromet? L-2- (hydro? Met? L) phen? L1-2,3,4,6-tetra-O- acet? l-ß-D-qlucop? ranosa Under a stream of nitrogen, to a solution of 1, 1 -anh? dro-1-C- [2, 5-b? S (hydrox? Met?) Phen? L] -β-D-glucopyranose (100 mg, 0 34 mmol) in DMSO (0 19 ml, 2 68 mmol), chlorotin-methylsilane (1 14 μl, 0 91 mmol) was added dropwise at room temperature and the mixture was stirred at the same temperature for 1.5 hours. To the crude product obtained by distillation of the volatile components, N-methylmorphone (0.74 ml, 6 70 mmole), 4-d? Methylampyrinone (41 mg, 0 34 mmole) and acetic anhydride (0 32 ml, 3 35 mmole) and the mixture was stirred on ice for 1 hour and 10 minutes After the addition of saturated aqueous sodium chloride (1 ml) and water (1 ml), the reaction mixture was extracted with ethyl acetate (10 ml). The organic layer was washed with water (15 ml). and saturated aqueous sodium chloride (1 ml), dried over sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (developing solution = ethyl acetate n-hexane (1 2 5). )) stop r the title compound (122 9 mg, 76%) 1 H-NMR (CDCl 3) d 1 74 (3 H, s), 2 O 1 (3 H, s), 2 05 (1 H, s), 2 08 (3 H, s), 3 99-4 08 (1 H, m), 4 24-4 37 (2H, m), 4 61 (2H, s), 5 12-5 34 (3H, m), 5 56-5 67 (2H, m), 7 22-7 28 (1 H, m), 7 38-7 47 (2H, m) 3) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-b? Phen? L) -met? L-2- (hydro? Met? L) phen? P-2, 3,4,6-tetra-O-acet? L-ß-D-qlucop? Canosa Under a stream of nitrogen, to a solution of 1, 1 -anh? Dro-1-C- [5-chloromet? L- 2- (H? Drox? Met? L) phen? L] -2,3,4,6-tetra-O-acet? L-β-D-glucopyranose (250 mg, 0 516 mmol) in toluene ( 2.5 ml), tnphenylphosphine (20 mg, 0.078 mmol), palladium acetate (8.0 mg, 0.039 mmol), 4-biphenylboronic acid (204 mg, 1.03 mmol) and potassium phosphate (219 mg) were added. , 1.03 mmol) The reaction mixture was heated to 80 ° C and stirred for 15 hours. After the addition of water and ethyl acetate, the reaction mixture was washed with saturated aqueous sodium chloride. The organic layer was dried over Magnesium sulfate, filtered and then evaporated under reduced pressure to remove the solvent The residue was purified by flash column chromatography (developing solution = ethyl acetate hexane (1 2) to give the title compound (280 mg, 90%) 1 H-NMR (CDCl 3) d 1 71 (3 H, s), 2 00 (3 H, s), 2 05 (3 H, s), 2 06 (3H, s), 4 04 (2H, s), 4 25-4 36 (2H, m), 5 17 (2H, dd, J = 12 5, 25 8Hz), 5 26-5 33 (2H, m ), 5 58-5 63 (2H, m), 7 15-7 34 (6H, m), 7 39-7 44 (2H, m), 7 51 -7 58 (4H, m) 4) Synthesis of 1, 1 -anh? Dro-1-C-5- (4-b? Phen?) Met? L-2- (hydro? Met?) Phen? Ll-b-D- qlucopranose To a solution of 1, 1 -anh? dro-1-C- [5- (4-b? phen?) -met? l-2- (hydrox? met? l) phen? l ] -2,3,4,6-tetra-O-acet? L-ß-D-glucopyranose (280 mg, 0 465 mmoles) in methanol (30 mL), potassium carbonate (45 mg, 326 mmol) was added and the mixture was stirred at room temperature for 1 hour. After the addition of water, the reaction mixture was extracted with ethyl acetate. ethyl The organic layer was washed with saturated aqueous sodium chloride and dried over magnesium sulfate. After filtration, the solvent was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (developing solution = methylene methylene chloride ( 15)) to give the title compound (84 mg, 42%) 1 H-NMR (CD 3 OD) d 3 40-3 51 (1 H, m), 3 63-3 69 (1 H, m), 3 75 -3 84 (4H, m), 4 04 (2H, s), 5 1 1 (2H, m), 7 20-7 31 (6H, m), 7 37-7 42 (2H, m), 7 50 -7 58 (4H, m) MS (ESI +) 457 [M + Na] + EXAMPLE 10 1, 1-Anhydro-1-C-f5- (4 - ((S) -tetrahydrofuran-3-yloxy) phenyl) -methyl-2- (hydroxymethyl) phenyl-β-D-glucopyranose 1) Synthesis of 1,1-anhydro-1-C- [5- (4-benzyl) -phenyl) -methyl-2- (hydroxyl) phenol. -2,3,4,6-tetra-O-acet? L-ß-D-qlucop? Canosa Using 1, 1-anhydro-1-C- [5-chloromet? L-2- (hydro? ? met?) fen? l] -2,3,4,6-tetra-O-acet? l-ß-D-glucopyranose and appropriate reagents, the same procedure as that used in example 9 was repeated for give the title compound 1 H-NMR (CDCl 3) d 1 70 (3 H, s), 2 00 (3 H, s), 2 05 (3 H, s), 2 07 (3 H, s), 3 94 (2 H, s), 4 01 - 4 09 (1 H, m), 4 23-4 36 (2H, m), 5 04 (2H, s), 5 15 (2H, dd, J = 12 6, 25 9Hz), 5 24-5 33 ( 1 H, m), 5 53-5 66 (2H, m), 6 85-6 94 (2H, m), 7 03-7 47 (10H, m) MS (ESI +) 655 [M + Na] + 2) Synthesis of 1,1-anhydro-1-C- [5- (4-h? Drox? Phen?) Met? L-2- (hydrox? Met? L) phen? P-2 , 3,4,6-tetra-O-acet? L-ß-D-qlucop? Canose To a solution of 1,1-anhydro-1-C- [5- (4-benz? Lox? Fen? l) met? l-2- (hydrox? met? l) phen? l] -2,3,4,6-tetra-O-acet? l -ß-D-glucopyranose (250 mg, 0 57 mmol) in a mixture of THF (7 ml) and methanol (7 ml), 10% palladium catalyst (200 mg) was added. Under a hydrogen atmosphere, the reaction mixture was stirred at 35 ° C for 12 hours and then filtered to remove the catalyst. After distilling off the solvent under reduced pressure, the resulting residue was purified by silica gel column chromatography (developing solution = ethyl acetate n-hexane (11) to give the title compound). titer (193 mg, 90%) 1 H-NMR (CDCl 3) d 1 70 (3 H, s), 2 00 (3 H, s), 2 05 (3 H, s), 2 07 (3 H, s), 3 93 ( 2H, s), 4 01 -4 09 (1 H, m), 4 23-4 36 (2H, m), 4 65 (1 H, s), 5 15 (2H, dd, J = 12 2, 25 9Hz), 5 24-5 33 (1 H, m), 5 53-5 66 (2H, m), 6 72-6 78 (2H, m), 6 98-7 05 (2H, m), 7 11 -7 24 (3H, m) MS (ESF) 565 [M + Na] + 3) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4 - ((S) -tetrah? Drofuran-3-? Lox?) - phen? L) -met? L-2- (hydrox? Met) ?) fen? ll-2,3,4,6-tetra-O-acet? l-β-D-qlucopranose To a solution of 1, 1-anhydr-1-C- [5- ( 4-h? Drox? Phen?) Met? L-2- (hydrox? Met? L) phen? L] -2,3,4,6-tetra-O-acet? L-ß-D- glycopyridase (190 mg, 0 35 mmol) in DMF (3 ml), tetrahydrofuran-3-ethyl ester of (R) -p-toluenesulfonic acid (102 mg, 0 42 mmol) and cesium carbonate ( 137 mg, 0 42 mmol) were added and the mixture was stirred at room temperature for 12 hours After the addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over sodium sulfate After filtration, the solvent was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (developing solution = ethyl acetate n-hexane (1-2)) to give the title compound (170 mg, 79%) 1 H-NMR (CDCl 3) d 1 71 (3 H, s), 2 00 (3 H, s), 2 04 ( 3H, s), 2 07 (3H, s), 2 12-2 21 (2H, m), 3 84-4 08 (7H, m), 4 22-4 36 (2H, m), 4 85-4 93 (1 H, m), 5 16 (2H, dd, J = 12 5, 25 7Hz), 5 24-5 33 (1 H, m), 5 53-5 66 (2H, m), 6 74- 6 81 (2H, m), 7 01 -7 10 (2H, m), 7 1 1 -7 19 (2H, m), 7 23 (1 H, s) MS (ESF) 635 [M + Na] + 4) Synthesis of 1,1-anhydro-1-C- [5- (4 - ((S) -tetrah? Drofuran-3-ylox?) - phen? L) -met? L-2- (h ? drox? met?) fen? l] -β-D-qlucop? canosa Using 1, 1 -anhydro-1-C- [5- (4 - ((S) -tetrah? drofuran-3? lox? ) fen? l) -met? l-2- (hydrox? met? l) phen? l] -2,3,4,6-tetra-O-acet? l -ß-D-glucopyranose and reagents The same procedure as that used in Example 9 was repeated to give the title compound 1H-NMR (CD3OD) d 2 00-2 28 (2H, m), 3 39-3 49 (1 H, m), 3 60- 3 98 (1 1 H, m), 4 92-5 00 (1 H, m), 5 10 (2H, m), 6 76-6 84 (2H, m), 7 08-7 15 ( 2H, m), 7 17-7 25 (3H, m) MS (ESI +) 467 [M + Na] + EXAMPLE 11 1, 1-Anhydro-1 -C-r5- (4 - ((R) -tetrahydrofuran-3-yloxy) phenyl) -methyl-2- (hydroxymethyl) phenyl-β-D-glucopyranose Using 1, 1 -anh? Dro-1-C- [5-chloromet- l-2- (hydrox? Met? L) phen? L] -2,3,4,6-tetra-O-acet? l-β-D-glucopyranose and appropriate reagents, the same procedure as that used in Example 10 was repeated to give the title compound 1 H-NMR (CD 3 OD) d 2 01 -2 29 (2H, m), 3 39-3 49 (1 H, m), 3 60- 4 01 (I1 H, m), 4 92-5 00 (1 H, m), 5 10 (2H, m), 6 77-6 84 (2H , m), 7 08-7 16 (2H, m), 7 17-7 25 (3H, m) MS (ESI +) 467 [M + Na] + EXAMPLE 12 1, 1 -Anhydro-1-C- [5- (4-ethynylphenyl) methyl-2- (hydroxymethyl) phenin- (YD-glucopyranose 1) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-tpfluoromethanesulfon? Lox? Phen? L) met? L-2- (hydro? Met? L) phen? L-2 , 3,4,6-tetra-O-acet? L-ß-D-qlucop? Canosa 1, 1 -Anh? Dro-1-C- [5- (4-hydrox? Phen?) Met? l-2- (hydroxylmethyl) phen? l] -2,3,4,6-tetra-O-acet? l-β-D-glucopyranose synthesized in Example 10 (185 mg, 0 341 mmoles) was dissolved in anhydrous methylene chloride (50 ml). To this solution, under a stream of nitrogen, pipdine (0.083 ml, 11.0 mmol) was added at room temperature, and anhydride was further added dropwise. of trifluoromethanesulfonic acid (0 086 ml, 0 51 1 mmol) The reaction mixture was stirred for 2 hours at room temperature. After distilling off the solvent under reduced pressure, the resulting residue was purified by flash column chromatography (developing solution = acetate ethyl ether n-hexane (11)) to give the title compound (217 mg, 94%) 1 H-NMR (CDCl 3) d 1 70 (3H, s), 2 00 (3H, s), 2 05 (3H , s), 2 07 (3H, s), 3 97-4 15 (3H, m), 4 23-4 37 (2H, m), 5 17 (2H, dd, J = 12 6, 25 9Hz), 5 24-5 33 (1 H, m), 5 54-5 66 (2H, m), 7 13-7 33 (7H, m) 2) Synthesis of 1, 1 -anh? Dro-1-C- [5- (4-tr? Met? Ls? Lan? Let? N? L? L?) Met? L-2- (h? Drox? Met ?) fen? n-2,3,4,6-tetra-O-acet? l-ß-D-qlucop? canosa Under a stream of nitrogen, 1, 1 -anh? dro-1-C- was mixed [5- (4-tpfluoromethanesulfon? Lox? Phen? L) met? L-2- (hydrox? Met? L) phen? L] -2,3,4,6-tetra-O-acetyl-β- D-glucopyranose (212 mg, 0 314 mmole), tpmethylsilylacetylene (0 089 ml, 0 628 mmole), tetylamine (0 2 ml, 1 44 mmole) and d? Chlorob? S (tpfen? Lfosf? N) palad? O (1 10 mg, 0 016 mmol) To this mixture, anhydrous DMF (3 ml) was added and the mixture was stirred at 90 ° C for 4 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer it was washed with saturated aqueous sodium chloride and dried over sodium sulfate. After filtration, the solvent was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (developing solution = ethyl acetate n-hexane (1 2). )) to give the title compound (95 mg, 48 %) 1 H-NMR (CDCl 3) d 0 23 (9H, s), 1 70 (3H, s), 2 00 (3H, s), 2 05 (3H, s), 2 07 (3H, s), 3 93-4 08 (3H, m), 4 23-4 37 (2H, m), 5 16 (2H, dd, J = 12 6, 25 2Hz ), 5 24-5 33 (1 H, m), 5 51-5 66 (2H, m), 7 04-7 18 (4H, m), 7 22 (1 H, s), 7 35-7 42 (2H, m) 3) Synthesis of 1, 1 -anh? Dro-1-C- [5- (4-et? N? Lfen? L) met? L-2- (hydro? Met? L) phen? P-b -D-qlucop? Ranosa Using 1, 1 -anh? Dro-1-C- [5- (4-tr? Met? L? L? Il? L? L? L?) Met? L-2- (h? drox? met?) fen? l] -2,3,4,6-tetra-O-acet? l -ß-D-glucopyranose and reagents The same procedure as the one used in Example 9 was repeated to give the title compound 1 H-NMR (CD 3 OD) d 3 40 (1 H, s), 3 41 -3 49 (1 H, m), 3 62 -3 70 (1 H, m), 3 72-3 85 (4H, m), 4 01 (2H, s), 5 1 1 (2H, m), 7 17-7 25 (5H, m), 7 34-7 40 (2H, m) MS (ESf) 383 [M + 1] + EXAMPLE 13 1, 1 -anhydro-1 -C-f5- (4-hydroxyphenyl) methyl-2- (hydroxymethyl) phenylH-β-D-glucopyranose Using 1, 1 -anhydro- 1 -C- [5- (4-hydrox? Phen?) Met? L-2- (hydrox? Met? L) phen? L] -2.3.4 6-tetra-O-acet? L-β-D-glucopyranose synthesized in Example 10 and appropriate reagents, the same procedure as that used in Example 9 was repeated to give the title compound 1H-NMR (CD3OD) d 3 39-3 52 (1 H, m), 3 61 -3 71 (1 H, m), 3 72-3 85 (4H, m), 3 90 (2H, s), 5 10 (2H, m ), 6 64-6 74 (2H, m), 6 97-7 06 (2H, m), 7 15-7 25 (3H, m) MS (ESI +) 397 [M + Na] + EXAMPLE 14 1.1 -Anhydro-1-C-f5- (4-pyrazol-1-yl-phenyl) methyl-2- (hydroxymethyl) phenan-β-D-glucopyranose 1) Synthesis of 4-p? Razol-1 -? L-phen? Lboron? Co acid Under a stream of nitrogen, to a solution of 1 - (4-bromophen? L) -1 Hp? Razol (995 mg, 4 46 mmoles) in anhydrous THF (12 ml), a hexane solution of n-butyl-thio (1 6 M, 2 79 ml, 466 mmol) was added dropwise at -78 ° C after stirring thereto. temperature for 1 hour, this solution was added dropwise at -78 ° C to a solution of tpmethyl borate (1 07 ml, 9 37 mmol) in anhydrous THF (8 ml) After stirring at the same temperature for 1 hour , the reaction mixture was stirred at room temperature for one day and one night. After the addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over magnesium sulfate After filtration, the solvent was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography ( development phase = methylene chloride methanol (50 1)) to give the title compound (314 mg, 37%) 1 H-NMR (CDCl 3) d 6 45-6 50 (1 H, m), 7 52-7 64 (4H, m), 7 72 (1 H, d, J = 1 5Hz), 7 89 (1 H, d, J = 2 3Hz) MS (ESI +) 189 [M + 1] + 2) Synthesis of 1,1-anhydro-1-C- [5- (4-p? Razol-1-? Lfen? L) met? L-2- (hydro? Met? L) phen? ll-ß-D-qlucop? ranosa Using 4-p? razol-1-? l-phen? lboron? co acid, 1,1-anhydro-1-C- [5-chloromet? l-2- ( H? drox? met?) fen? l] -2,3,4,6-tetra-O-acet? l-β-D-glucopyranose and appropriate reagents, the same procedure used in Example 9 was repeated to give the title compound 1H-NMR (CD3OD) 340-352 (1H, m), 361-370 (1H, m), 372-385 (4H, m), 405 (2H, s), 511 (2H, dd, J = 126, 198Hz), 646-652 (1H, m), 719-739 (5H, m), 759-772 (3H, m), 812-817 (1H, m) MS (ESI +) 425 [ M + 1] + EXAMPLE 15 1, 1 -Anhydro-1 -C-r5- (4-methoxyphenyl) ethyl-2- (hydroxymethyl) phenyl-β-D-glucopyranose 1) Synthesis of 1,1-anhydro-1-C- [5- (4-methox? Phen? L) et? L-2- (hydro? Met? L) phen? L] -2, 3,4,6-tetra-O-acet? L-ß-D-qlucopyranose Under a stream of nitrogen, to a solution of 1,1-anh? Dro-1-C- [5-chloromet? L-2- (h? drox? met? l) fen? l] -2,3,4,6-tetra-O-acet? l-β-D-glucopyranose (200 mg, 041 mmol) in anhydrous THF (10 ml ), a solution in THF of lithium tetrachlorocuprate (01 M, 0124 ml, 0012 mmol) and N-methylpyrrolidinone (016 ml, 164 mmol) were added dropwise at room temperature. A THF solution of 4- bromide methoxybenzylmagnesium (0 25 M, 1 72 ml) was added dropwise over 5 minutes at room temperature. The reaction mixture was stirred at room temperature for one day and one night. After the addition of 2N hydrochloric acid (2 ml), the The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over magnesium sulfate. After filtration, the solvent was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography ( development = ethyl acetate h-hexane (2 3)) to give the title compound (13 mg, 6%) 1 H-NMR (CDCl 3) d 1 73 (3 H, s), 2 O 1 (3 H, s), 2 05 (3H, s), 2 08 (3H, s), 2 80-2 95 (4H, m), 3 79 (3H, s), 4 01 -4 07 (1 H, m), 4 27-4 37 (2H, m), 5 13 (1 H, d, J = 12 3 Hz), 5 21 (1 H, d, J = 12 3 Hz), 5 27-5 34 (1 H, m), 5 57-5 67 (2H, m), 6 80 (2H, d, J = 8 6Hz), 7 07 (2H, d, J = 8 6Hz), 7 14 (2H, s), 7 25-7 26 (1 H, m) 2) Synthesis of 1, 1 -anh? Dro-1 -C- [5- (4-methox? Phen? L) et? L-2- (hydrox? Met? L) phen? P-b-D -qlucopranose Using 1, 1 -anh? dro-1 -C- [5- (4-methox? phen? l) et? l-2- (hydrox? met? l) phen? l] -2 , 3,4,6-tetra-O-acet? L-ß-D-glucopyranose and appropriate reagents, the same procedure as that used in Example 9 was repeated to give the title compound 1 H-NMR (CD3OD ) 2 70-2 90 (4H, m), 3 38-3 44 (1 H, m), 3 57-3 78 (8H, m), 5 02 (1 H, d, J = 12 3Hz), 5 07 (1 H, d, J = 12 3 Hz), 6 74 (2 H, d, J = 8.7Hz), 7.03 (2H, d, J = 8.7Hz), 7.10 (2H, m), 7.15 (1H, s). MS (ESI +): 402 [M] + Tables 1 -1 and 1 -2 show the structural formulas of the compounds prepared in the previous examples. The compounds listed in Tables 1-3 to 1-8 can also be easily prepared in the same manner as shown in the above examples or production schedules with or without minor modifications obvious to those skilled in the art.

TABLE 1-1 TABLE 1-2 TABLE 1-3 TABLE 1-4 TABLE 1-5 TABLE 1-6 TABLE 1-7 TABLE 1-8 TABLE 1-9 EXAMPLE OF TEST 1 Evaluation of inhibitory activity against methyl-α-D-glucopyranoside absorption of human Na + -glucose cotransporter (SGLT1 and SGLT2) 1) Construction of expression vector of human SGLT1 cDNA of human SGLTI was amplified by PCR with a cDNA library derived from human small intestine (Clontech) as a template, synthetic DNA primers and KOD + DNA polymerase (Toyobo Co, Ltd, Japan ) The amplified cDNA was inserted into pcRII-Topo vector using a Topo TA double cloning promoter kit (Invitrogen) Competent E coli cells (Invitrogen, TOP10) were transformed with the plasmid vector, cultured in LB medium containing ampicin ( 50 mg / l) for Grow ampicillin resistant clones The plasmid vector containing human SGLTI cDNA was purified from the clone in a standard manner (see Maniatis et al, Molecular Cloning) human SGLTI cDNA to which restriction enzyme recognition sites were added (Eco Rl at the 5 'end, Hmd lll at the 3' end) was amplified by PCR with the plasmid vector as a template, synthetic DNA primers containing an additional restriction enzyme recognition site, and KOD + DNA polymerase This cDNA amplified was digested with Eco R1 and Hind III and ligated to the expression vector pcDNA3 1 (-) (Invitrogen) digested with Eco R1 and Hind III by a rapid DNA ligation kit (Roche Diagonostics) Competent E coli cells (Invitrogen, DH5a) were transformed with the bound expression vector and grown in LB medium containing ampicillin. The expression vector of human SGLT1 was purified from the amphibious clone. Cylindrical in a standard way 2) Construction of expression vector of human SGLT2 cDNA of human SGLT2 was amplified by PCR with a cDNA library derived from human (Clontech) as a template, synthetic DNA primers and KOD + pohmeres DNA Amplified cDNA was inserted into vector pcRII- Topo using a double Topo TA cloning promoter team E coli competent cells (TPO10) were transformed with the plasmid vector, cultured in LB medium containing ampicillin (50 mg / l) to grow resistant clones. ampicihna The plasmid vector containing human SGLT2 cDNA was purified from the clone in a standard human SGLT2 cDNA to which restriction enzyme recognition sites were added (Xho I at the 5 'end, Hmd lll at the 3' end ) was amplified by PCR with the plasmid vector as a template, synthetic DNA primers containing an additional restriction enzyme recognition site, and KOD + DNA polymerase This amplified cDNA was digested with Xho / and Hmd III, and ligated to the vector of expression pcDNA3 1 (-) d? ger? do with Xho I and Hínd lll using a rapid DNA ligation kit Competent cells of E coli (DH5a) were transformed with the bound expression vector and grown in LB medium containing ampicillin The expression vector of human SGLT2 was purified from the ampicillin-resistant clone in a standard manner 3) Establishment of cell lines stably expressing human SGLT1 or human SGLT2 The expression vector of human SGLT1 or the expression vector of human SGLT2 was digested with the restriction enzyme Pvu I and transfected into CHO-K1 cells with FuGENE (Roche Diagonostics) After transfection, cells were cultured at 37 ° C in the presence of 5% CO2 for approximately 3 weeks in DMEM medium (Gibco) containing penicillin (50 U / ml, SIGMA), streptomycin (50 mg / l , SIGMA), geneticin (200 mg / l, Nacalai Tesque, Inc., Japan) and 20% fetal bovine serum to obtain genetic-resistant clones. Among these clones, the clones stably expressing human SGLT1 or human SGLT2 were selected by evaluating the sodium-dependent absorption activity of sugar (methyl-a-D-glucopyranoside) 4) Evaluation of inhibitory activity against methyl-aD-qlucopyranoside absorption Cell lines stably expressing CHO from human SGLT1 or human SGLT2 were seeded in 96-well plates at a density of 30000 to 40,000 cells / well and cultured for 4 hours. at 6 days The medium in these plates was removed and replaced by 150 μl / well of pretreatment pH buffer (i.e., a pH regulator containing 140 mM choline chloride, 2 mM potassium chloride, 1 mM calcium chloride, 1 mM magnesium chloride, 10 mM acid 2- [4- (2-hydroxyl et? l) -1-p? peraz? n? l] ethanesulfon? co and tr? s ( h? drox? met? l) ammonethane, pH 7 4), and the plates were incubated at 37Â ° C for 20 minutes The pretreatment pH regulator on the plates was removed, replaced by 50 μl / well regulator Fresh pretreatment pH, and plates were incubated at 37 ° C for 20 minutes Met? laD- (U-14C) glucopranoside (6 3 ml, Amersham Pharmacia Biotech, 200 mCi / l) was added and mixed with 100 ml of pH regulator (i.e., a pH regulator containing 140 mM sodium chloride, 2 mM potassium chloride, 1 mM calcium chloride, 1 mM magnesium chloride, 1 M of methyl-α-D-glucopyranoside, 10 mM of acid [4- (2-hydroxyl et? l) -1-p? peraz? n? l] ethanesulfon? co and tr? s (hydrox? met? l) ammonethane, pH 7 4), which was used as an absorption pH regulator The test compounds were dissolved in the absorption pH regulator and these test compound solutions were used to evaluate inhibitory activity. The absorption pH regulator without a test compound was used as a control solution. even, to be used in the measurement of baseline absorption in the absence of sodium, a sodium-free solution was prepared in the same manner to contain 140 mM choline chloride instead of sodium chloride. The pretreatment pH regulator was removed from each well of the plates and was replaced by 35 μl / well of test compound solutions, control solution or sodium-free solution, and the plates were incubated at 37 ° C for 45 minutes. The solutions were removed and replaced by 300 μl / Wash pH regulator well (ie, a pH regulator containing 140 mM choline chloride, 2 mM potassium chloride, 1 mM calcium chloride, 1 mM chloride of magnesium, 10 mM of methyl-aD-glucopyranoside, 10 mM of acid 2- [4- (2-h? drox? et? l) -1-p? peraz? n? l] ethanesulfon? co and tr? s (h? drox? met? l) ammonethane, pH 7 4) The washing pH regulator was removed immediately This washing procedure was repeated once more, and a cell lysis solution (1 M hydroxide) sodium, 0 1% sodium lauryl sulfate) was added in a volume of 30 μl per well to solubilize the 2 M hydrochloric acid cells (15 μl) was added to the cell lysate in each well, and 40 μl of the resulting solution was transferred to a LumaPlate (Packard) The LumaPlate was left overnight at room temperature to evaporate the solvent Samples on the plate were measured for radioactivity with a TopCount NXT (Packard) Assuming that the value obtained by subtracting the baseline absorption level from the absorption level of the control sample was set at 100%, the concentration required for the test compounds to cause 50% inhibition of the absorption level (Cl50 value) were calculated from the concentration-dependent inhibition curve using ELfit ver 3 As a result, it was found that the compounds of the present invention show a remarkable inhibitory effect on SGLT2. The following table shows the Cl50 values of representative compounds of the present invention, as measured for inhibition of SGLT2.

TABLE 2 Ap industrial property The present invention allows to provide spirocetal compounds, prodrugs thereof or pharmaceutically acceptable salts thereof, which have an excellent inhibitory effect on the activity of SGLT2. The compounds of the present invention are also effective as prophylactic or therapeutic agents. for diabetes, diabetes-related disease or diabetic complications

Claims (15)

1. NOVELTY OF THE INVENTION
2. CLAIMS 1 .- A compound of the formula (I): wherein R1, R2, R3 and R4 are each independently selected from a hydrogen atom, a C6 alkyl group which can be substituted with one or more Ra, a C7-C14 aralkyl group which can be substituted with one or more Rb, and -C (= O) Rx; Rx represents an alkyl group of Ci-Ce which can be substituted with one or more Ra, an aryl group which can be substituted with one or more Rb, a heteroaryl group which can be substituted with one or more Rb, an alkoxy group of C Ce that can be substituted with one or more Ra, or -NReRf; Ar1 represents an aromatic carbocyclic ring that can be substituted with one or more Rb, or an aromatic heterocyclic ring that can be substituted with one or more Rb; Q represents - (CH2) m- (L) p- or - (L) p- (CH2) Y m represents an integer selected from 0 to 2, n represents an integer selected from 1 and 2, and p represents an integer selected from 0 and 1, L represents -O-, -S- or -NR5-, R5 is selected from a hydrogen atom, an alkyl group of C Cß which can be substituted with one or more Ra, and -C (= O) Rx, A represents an aplo group that can be substituted with one or more Rb or an hetero group that can be substituted with one or more Rb, where the group aplo or group hetero-tile can form a fused ring together with the aromatic carbocyclic ring or the aromatic heterocyclic ring, Ra is independently selected from a halogen atom, a hydroxyl group, a cyano group, a nitro group, a carboxyl group, an alkoxy group of CrC6 which it can be substituted with one or more Rc, an aplo group that can be substituted with one or more Rd, an aploxi group that can be substituted with one or more Rd, a heterolate group that can be substituted with one or more Rd, a group heteroaploxy that can be substituted with one or more Rd, a mercapto group, a alkylthio group of CrC6 which can be substituted with one or more Rc, an alkylsulfinyl group of Ci-Cß which can be substituted with one or more Rc, an alkylsulfonyl group of C Cß which can be substituted with one or more Rc, -NRfRg, a C 1 β alkoxycarbonyl group which can be substituted with one or more R c, and a C C β alkylcarbonyl group which can be substituted with one or more R c, R b is independently selected from a C C β alkyl group which can be substituted with one or more Rc, a C3-C8 cycloalkyl group which can be substituted with one or more Rc, a C2-C6 alkenyl group which can be substituted with one or more Rc, a C2-C6 alkynyl group which can be substituted with one or plus Rc, an aralkyl group of C7-C? 4 which can be substituted with one or more Rd, a halogen atom, a hydroxyl group, a cyano group, a nitro group, a carboxyl group, an alkoxy group of C Ce which can be substituted with one or more Rc, an aplo group that can be substituted with one or more Rd, an aploxi group that can be substituted with one or more Rd, a heteropole group that can be substituted with one or more Rd, a group heteroaploxy which can be substituted with one or more Rd, a mercapto group, a CC alkylthio group which can be substituted with one or more Rc, an alkylsulfinyl group of Ci-Ce which can be substituted with one or more Rc, an alkylsulfonyl group of d-Ce which can be substituted with one or more Rc, -NRfRg, an alkylcarbonyl group of C Cß which can be substituted with one or more Rc, a C 1 β alkoxycarbonyl group which can be substituted with one or more Rc, alkylenedioxy group of C ^ Cs, a heterocyclic group, and a heterocyclyloxy group, Rc is selected independently of a halogen atom, a hydroxyl group, a cyano group, a nitro group, a carboxyl group, an alkoxy group of C Ce, an aplo group that can be substituted with one or more Rd, an aploxy group that can be substituted with one or more Rd, a heteroaryl group that can be substituted with one or more Rd, a hetero-aploxy group which can be substituted with one or more Rd, an amino group, an alkylamino group of CrC6, and a group d? - (alkyl ? lam? of CrC6), Rd is independently selected from an alkyl group of C Ce which can be substituted with one or more halogen atoms, a C7-C? aralkyl group, a halogen atom, a hydroxyl group, a cyano group, a nitro group, an amino group, a group alkylamino of C Ce, and a group d? - (alkylamine of CrC6), Re represents a hydrogen atom, an alkyl group of C Ce which can be substituted with one or more Rc, an aplo group which can be substituted with one or more Rd, or a heteroaryl group which can be substituted with one or more Rd, Rf represents a hydrogen atom or an alkyl group of C Ce which can be substituted with one or more Rc, and Rg represents a hydrogen, an alkyl group of C Ce which can be substituted with Rc, a C6 alkylcarbonyl group which can be substituted with one or more Rc, an aplo group which can be substituted with one or more Rd, a heterolalk group which can be substituted with one or more Rd, a carbamoyl group, a C Cß alkoxycarbonyl group which can be substituted with one or more Rc, or a C6 C alkylsulfonyl group which can be substituted with one or more Rc, or Re and Rf, or Rf and Rg can form a 4- to 7-membered heterocyclic ring together with the nitrogen atom to which they are attached. linked, or a prodrug thereof, or a pharmaceutically acceptable salt thereof 2 - The compound according to claim 1, further characterized in that R1, R2, R3 and R4 are each independently selected from a hydrogen atom and -C ( = O) Rx, and Rx is preferably an alkyl group of C -? - C6 which can be substituted with one or more Ra, or a C C? Alkoxy group which can be substituted with one or more Ra, or a prodrug thereof , or a pharmaceutically acceptable salt thereof
3. 3 - The compound according to claim 1, further characterized in that R1, R2, R3 and R4 are each a hydrogen atom, or a prodrug thereof, or a pharmaceutically acceptable salt thereof
4. 4-The compound according to any of claims 1 to 3, further characterized in that Ar1 is a phenylene group or a thienylene group, each of which can be substituted with one or more Rb, or a prodrug thereof, or a pharmaceutically acceptable salt thereof
5. 5- The compound according to any of claims 1 to 4 , further characterized in that m is 1 and p is 0, or a prodrug thereof, or a pharmaceutically acceptable salt thereof
6. 6-The compound according to any of claims 1 to 4, further characterized in that n is 1, or a prodrug of the same, or a pharmaceutically acceptable salt thereof
7. 7 - The compound according to any of claims 1 to 6, further characterized in that Ar1 has the substituent -QA in its αt. as a ring that is 2 atoms apart from the ring atom directly attached to the substituted glucitol group, or a prodrug thereof, or a pharmaceutically acceptable salt thereof
8. 8 -. 8 - The compound according to any of claims 1 to 7, further characterized in that it is represented by the formula (la) or a prodrug thereof, or a pharmaceutically acceptable salt thereof
9. 9 - A compound selected from 1,1 -anh? dro-1-C- [5- (4-et? lfen? l) met? l-2- ( hydrox? met?) phen? l] -β-D-glucopyranose, 1, 1 -anhydro-1-C- [5- (2-benzoth? ofen? l) met? l-2- ( h? drox? met?) phen? l] -β-D-glucopyranose, 1, 1-anhydro-1-C- [5- (4-methox? phen?) met? l-2 - (H? drox? met? l) phen? l] -ß-D-glucop? ranosa, 1, 1 -anh? dro-1-C- [5- (4-? soprop? lfen? l) met? l-2- (H? drox? met? l) phen? l] -β-D-glucopyranose, 1, 1 -anh? dro-1-C- [5- (4-c? cloprop? lfen? l) met-l-2- (hydroxylmethyl) phenol] -β-D-glucopyrane, 1, 1 -anth-1-C- [5- (4-n- prop? lfen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucop? ranosa, 1, 1 -anh? dro-1-C- [5- ( 4-et? Lfen? Lox?) - 2- (hydrox? Met? L) phen? L] -β-D-glucopyranose, 1, 1 -anh? Dro-1-C- [5- ( 4-et? Lfen? L) met? L-2- (2-h? Drox? Et? L) t? Ofen-3-? L] -β-D-glucop? Ranose, 1, 1 -anh? -1-C- [5- (4-b? Phen?) Met? L-2-hydrox? Met? L] phen? L] -β-D-glucopyranose 1, 1 -anh? -1 -C- [5- (4 - ((S) -tetrah? Drofuran-3-? Lox?) Phen? L) met? L-2- (hydrox? Met? L) phen? L] - ß-D-glucopi ranosa, 1, 1 -anh? dro-1 -C- [5- (4 - ((R) -tetrah? drofuran-3-? lox?) fen? l) met? l-2- (hydrox? met?) phen? l] -β-D-glucopyranose, 1, 1 -anh? dro-1-C- [5- (4-et? n? lfen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucop? ranosa, 1,1-anhydro-1-C- [5- (4-h? Drox? Phen?) Met? L-2- (hydro? Met? L) phen? L] -β-D -glucop? ranosa, 1, 1 -anh? dro-1-C- [5- (4-p? razol-1?? lfen? l) met? l-2- (hydro? met?) fen ? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (4-methox? phen?) et? l-2- (hydrox? met? ) fen? l] -β-D-glucopyranose, 1, 1-anhydro-1-C- [5- (4-met? lfen? l.}. met? l-2- (hydro? ? met? l) phen? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (3-acetam? dofen?) met? l-2- (h drox? met?) fen? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (3,4-met? leod? ox? phen?) met? l-2- (hydroxylmethyl) phenol] -β-D-glucopyrane, 1,1-anhydro-1-C- [5- (4-c? anophen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (3,4-d? chlorofen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucopyranose, 1, 1 -anh? dro-1-C- [5- (4- ethoxy? phen?) met? l-2- (hydrox? met? l) phen? l] -β-D-glucopyranose, 1, 1 -anh? dro-1-C- [5- ( 4-tr? Fluoromet? Lfen? L) met? L-2- (hydrox? Met? L) phen? L] -β-D-glucopyranose, 1, 1 -anh? Dro-1-C- [5 - (4-tr? Fluorometox? Phen?) Met? L-2- (hydrox? Met? L) phen? L] -β-D-glucop? Reose, 1, 1-anhydr-1- C- [5- (4-me t? lsulfan? lfen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucopyranose, 1, 1 -anhydro-1-C- [5- ( 4-chlorophen? L) met? L-2- (hydro? Met? L) phen? L] -β-D-glucopyranose, 1, 1 -anhydro-1-C- [5- (naphthalene- 2-? L) met? L-2- (hydrox? Met? L) phen? L] -β-D-glucop? Hoosa, 1, 1 -anh? Dro-1-C- [5- (4 -h? drox? met? lfen? l) met? l-2- (hydrox? met? l) phen? l] -ß-D-glucop? ranosa, 1,1-anhydro-1-C - [5- (4-fluorophen? L) met? L-2- (hydrox? Met? L) phen? L] -β-D-glucopyrane, 1,1-anhydro-1-C - [5- (2-met? Lfen? L) met? L-2- (hydrox? Met? L) phen? L] -β-D-glucop? Hoosa, 1,1-anhydro-1 -C- [5- (3-met? Lfen? L) met? L-2- (hydrox? Met? L) phen? L] -β-D-glucopyranose, 1,1-anhydro -1-C- [5- (3-benz? Lox? Phen? L) met? L-2- (hydrox? Met? L) phen? L] -β-D-glucopyrane, 1,1-anhydro-1-C- [5- (2,4-d? Fluorophen?) Met? L-2- (hydro? Met? L) phen? L] -β-D- glucopyranose, 1,1-anhydro-1-C- [5- (4- (2-fluoroetyl) phen?) met? l-2- (hydro? met? l) phen? l] -β-D-glucopranose, 1,1-anhydro-1-C- [5- (p? r? d? n-3-? l) met? l-2- (hydro? ? l) phen? l] -β-D-glucopyrane, 1,1-anhydro-1-C- [5- (4-methanesulfon? lfen? l) met? l-2- (hydrox? ? met? l) fen? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (p? pd? n-4-? l) met? l-2 - (H? drox? met? l) phen? l] -β-D-glucopranose, 1,1-anhydro-1-C- [5- (1H-? ndol-2-? l) met ? l-2- (hydroxyl) phenol] -β-D-glucopyrane, 1,1-anhydro-1-C- [5- (3-hydrox? phen l) met-l-2- (hydroxylmethyl) phenol] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (4-v) ? n? lfen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (4 -metox? carbon? lfen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucop? ranosa, 1,1-anhydro-1-C- [ 5- (4-carbox? Phen?) Met? L-2- (hydrox? Met? L) phen? L] -β-D-glucop? Hoosa, and 1, 1 -anh? Dro-1 - C- [5- (4- (2,2-d? Fluoroet? L) phen? L) met? L-2- (hydro? Met? L) phen? L] -β-D-glucopyranose, 1 , 1-anhydro-1-C- [5- (4-et? Lfen? L) met? L-2- ( h? drox? met?) -4-met? lfen? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [5- (4- (2,2,2-tr ? fluoroet?) fen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucopyranose, 1,1-anhydro-1-C- [ 5- (4-et? Lfen? L) met? L-2- (hydrox? Met? L) p? Raz? N-3-? L] -β-D-glucop? Ranosa, 1,1- anhydro-1-C- [5- (4-acet? lfen? l) met? l-2- (hydrox? met? l) phen? l] -β-D-glucop? ranosa, and 1 , 1 -anh? Dro-1-C- [5- (4- (1-h? Drox? Et? L) phen? L) met? L-2- (hydro? Met? L) phen? L ] - ß-D-glucopyranose, or a prodrug thereof, or a pharmaceutically acceptable salt thereof
10. 10 -. 10 - A compound of the formula (Ib) OP3 (Ib) where n represents an integer selected from 1 and 2, Ar1 represents a aromatic carbocyclic ring which can be substituted with one or more Rb, or a aromatic heterocyclic ring that can be substituted with one or more Rb, W represents -O-Z or a halogen atom, Z represents an atom of hydrogen, an acyl group or a benzyl group, P1, P2, P3 and P4 are selected each independently of a hydrogen atom, an acyl group or a benzyl group, and Rb is as defined above
11. 1 1 - A pharmaceutical composition to be used as a inhibitor of Na + -glucose co-transporter, which comprises the compound according to any one of claims 1 to 9, or a prodrug thereof, or a pharmaceutically acceptable salt thereof
12. 12 -. 12 - A pharmaceutical composition for use in prevention or treatment of diabetes, hyperglymia diabetic complications induced for the same or obesity, which comprises the compound in accordance with any of claims 1 to 9, or a prodrug thereof, or a salt Pharmaceutically acceptable thereof
13. 13 - The pharmaceutical composition according to claim 12, further characterized in that diabetes is insulin dependent diabetes mellitus (type I diabetes) or non-insulin dependent diabetes mellitus (type II diabetes)
14. 14 - The use of the compound according to any of claims 1 to 9, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament useful for the prevention or treatment of diabetes, diabetic complications induced by hyperglycemia or obesity, in a patient
15. 15 - The use claimed in claim 14, wherein the diabetes is insulin-dependent diabetes mellitus (type I diabetes) or non-insulin dependent diabetes mellitus (type II diabetes)