TETRAZOLE GLYCOSIDES

This application claims the benefit of Indian Provisional Patent Application No. 1934/CHE/2008, filed August 11, 2008, which is herein incorporated by reference. Field of the Invention

The invention relates to tetrazole glycoside derivatives, which are inhibitors of Sodium dependent glucose co transporter (SGLT), particularly SGLT2.

Background of the Invention Diabetes is one of lifestyle-related diseases with the background of change of eating habit and lack of exercise. Hence, diet and exercise therapies are performed in patients with diabetes. Approximately 200 million people worldwide suffer from Type 2 diabetes mellitus (T2DM), which is characterized by hyperglycemia due to excessive hepatic glucose production and peripheral insulin resistance, the root causes of which are as yet not clearly understood. Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by impaired insulin secretion in response to glucose, increased hepatic glucose production, and decreased insulin-dependent glucose uptake in the peripheral tissues or insulin resistance. The prevalence of T2DM is reaching epidemic proportion with more than 194 million cases reported in 2003, expected to increase to 333 million by 2025 (Pharmacother.; 118(2): 181- 191; 2008). The prolonged hyperglycemia in combination with insulin resistance, causes microvascular and macrovascular damage, which is a cause of considerable morbidity and mortality. Although, diet and exercise are the cornerstones of treatment in order to correct obesity and hyperglycemia, about 40 to 60 % of newly treated patients do not respond adequately or fail to comply with diet. In recent years, development of new type antidiabetic agents has been progressing, which promote urinary glucose excretion and lower blood glucose level by preventing excess glucose reabsorption at the kidney (J. Clin. Invest., Vol. 79, pp. 1510-1515 (1987)). Sodium dependent glucose transporter-2 (SGLT2) is present in the S 1 segment of the kidney's proximal tubule, participates mainly in reabsorption of glucose filtrated through glomerular (J. Clin. Invest, Vol. 93, pp. 397-404

(1994)). Accordingly, inhibiting a human SGLT2 activity prevents reabsorption of excess glucose at the kidney, subsequently promotes excreting excess glucose though the urine, and normalizes blood glucose level. Therefore, fast development of antidiabetic agents, which have a potent inhibitory activity in human SGLT2 is desired. In addition, since such agents promote the excretion of excess glucose though the urine and consequently the glucose accumulation in the body is decreased, they are also expected to have a preventing or alleviating effect on obesity and a urinating effect. Furthermore, the agents are considered to be useful for various related diseases which occur accompanying the progress of diabetes or obesity due to hyperglycemia. Since SGLT-2 inhibitors do not stimulate insulin secretion; therefore, they would be expected to have a low hypoglycemia risk {Intl journal of clinical practice; 62 (8), 1279-1284, 2008).

In the recent past, many articles were published in various journals on SGLT inhibitors {Diabetes, 2008, 57, 1723-24; Diabetes, obesity and metabolism, 11,

2009, 79-88; and Diabetes, 1999, 48, 1794-1800). European journal of Pharmacology, 391 (2000), 183-192, Nature protocols, 2007, 2(6), 1356-59 described some preliminary assay methods to evaluate the compounds potential such as inhibition of Na+-glucose co transporter activity in brush border membrane vesicles (BBMVs) and Isolation of renal proximal tubular brush-border membranes.

It is thus believed SGLT2 inhibitors may be relevant with respect to diabetes, diabetic complications or obesity. PCT Publications Nos. WO 01//016147, WO

01/074835, WO 02/068439, WO 02/083066, WO 03/020737, WO 03/080635, WO

04/063209, WO 04/089967, WO 06//034489, WO 08/072726, WO 08/116195, WO 08/122014, WO 08/101939 and WO 08/144346; US patent application/patent Nos.

US 7,476,671, US 7,439,232, US 2006/0194809 and US 2008/0132563; EP patent application/patent Nos. EP 150621 IBl, EP 1224195B1, EP 1268502B1, EP 1268503A1, EP 1581543A4 and EP 1685147A4 disclose SGLT2 inhibitors, for treatment of various diseases mediated by SGLT2 inhibitors. Also some disclosures and publications on various aspects of SGLT are as follows: Biochem.Biophys Acta 1975 ,554,259-263; Diabetes, vol.48, (1999), 1794- 1800; IntJ.Med Sci.2007, (3)131-139; Biol. & Pharma.Bulletin, 2000, 23, 1434; British J.of pharmacology 2001, 32,578-586;

AmJ.Physiol.Endocrinol.Metab.2000.280, 535; Clin. & Experi. Pharmacology & physiology 2002, 9, 86; J.Med.cheml999, 42(26) 5311-5324; J.Med.chem2008, 51,

145-1149; Nature protocols 2007, 2(5), 356-1359; US 6,555,519; Bioorganic & Medicinal chemistry Letters 2003, 3, 269 - 2272; US 6,414,126 Bl; US 6,683,056 B2; International Journal of medical Sciences 2006, 3(3), 84-91; J.Clin.Invest.1994, 93,397-404; The Journal of Pharmacology and Experimental Therapeutics 2007, 320(1), 323-330; The Journal of Biological Chemistry 1995, 270 (49), 29365-29371; Life Sciences 2005; 76, 2655-2668; Bioorganic & Medicinal chemistry Letters 2005, 15, 2655 - 2668; The Journal of Biological Chemistry 1993, 268 (3), 1509- 1512; Tetrahedron Letters 2000; 41, 9213-9217; Life Sciences 2005, 76, 1039-1050; Biol. Pharm. Bull 2006, 29(1), 114-118; Bioorganic & Medicinal chemistry Letters

2003, 13, 2269 - 2272; Drugs of the future 2001, 26(8), 750; Drugs of the future

2004, 29, 461-466; Proc.Natl.Acad.Sci USA 2003, 100 (20); 11753-11758; Annu.Rev.Nutr. 1996, 16, 235; J.Bio.chem 1994, 219, 753; Diabetes 1997, 46, 1667; Trends in cell biogy 2001, 11, 173; Proc.Natl.Acad.Sci USA 1989, 86, 5748; Biol. & Pharma. Bull. 2000, 23, 1434; British J. Pharm 2001, 132, 578;

AmJ.physiol.Endcri.Metab.2000, 278, E-53; AmJ.physiol.Endcri.Metab.2000, 278, E-816; Bio chem.Biophy.Res.Commun.1999, 266, 252; Clin. & Experi. Pharmacology & physiology 2002, 29, 386; Chem. Pharm.Bulll996, 44, 1174-1180; and Chem. Pharm. Bull 1998, 46, 22-33; Chem. Pharm. Bull 1998, 46, 1545-1555. There still exists a need to discover better agents for therapeutic treatment of diseases, conditions and/or disorders inhibited by SGLT2 inhibitors.

Summary of the Invention The present invention relates to tetrazole glycoside compounds of the formula (1):

wherein,

X can be H, lower alkyl group, lower perfluoro alkyl group, aralkyl group, phenyl group, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxylgroup may be esterified);

Y can be

Ring A and B are independently can be selected from phenyl, naphthyl, heteroaryl, cycloalkyl or heterocyclyl which may contain 5 to 7 membered ring, which may contain 1 to 4 hetero atoms like N, O, S, SO or SO ₂ in the ring;

Z can be oxygen, methylene, (CH ₂ ) _n , dimethylmethylene, difluoromethylene, carbonyl, O-alkyl, S-alkyl, SO ₂ alkyl, -C(O)-NH-R ₁ R ₂ or Z may represent a bond between rings A and B; n can be an integer 0-3 ;

Y also can be _s substituted or unsubstituted aryl group more particularly substituted or unsubstituted phenyl group, substituted or unsubstituted aryl-C(O)-, substituted or unsubstituted aryl- CH ₂ -, or substituted or unsubstituted aryloxy-CH2-, where in substituents are Ri and R ₂ ; Ri and R ₂ are independently can be selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl, Ci _-6 -alkyl, C _2- β alkynyl, C _3-6 cycloalkyl, Ci-C ₄ alkylcarbonyl, aryl carbonyl, heteroarylcarbonyl, amino carbonyl, Ci- ₄ -alkylaminocarbonyl, hydroxyl, cyano, Ci _-4 alkyl sulphonylamino, arylsulphonylamino, Ci- β alkoxy, C _3-7 cycloalkoxy, aryloxy, aralkyloxy, aryloxyalkyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified); R ₃ and R ₄ are independently can be selected from hydrogen, alkyl, halo, perfluoroalkyl, CN, OH, O-alkyl, O-cycloalkyl, phenyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D- glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified);

R ₅ can be alkyl, or perfluoroalkyl.

Pharmaceutically acceptable salts of the compounds of the formula (1) are also contemplated. Likewise, pharmaceutically acceptable solvates, including hydrates, of the compounds of the formula (1) are contemplated.

It should be understood that the formula (1) structurally encompasses all positional isomers, stereo isomers, including enatiomers and diastereomers that may be contemplated from the chemical structure of the genus described herein. Also contemplated are prodrugs of the compounds of the formula (1), including ester prodrugs.

According to one embodiment, there is provided a compound of formula (1), wherein X is O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxylgroup may be esterified).

According to one embodiment, there is provided a compound of formula (1), wherein X is substituted or unsubstituted alkyl. In this embodiment, preferably alkyl is methyl or ethyl. According to one embodiment, there is provided a compound of formula (1), wherein Y is substituted or unsubstituted aryl. In this embodiment, preferably aryl is phenyl.

According to one embodiment, there is provided a compound of formula (1), wherein Y is substituted or unsubstituted aryl-C(O)-, substituted or unsubstituted aryl-CH2-, or substituted or unsubstituted aryloxy-CH ₂ - . In this embodiment, preferably aryl is phenyl.

According to one embodiment, there is provided a compound of formula (1),

wherein Y is In this embodiment, preferably A is phenyl, B is phenyl, and

Z is CH ₂ . According to one embodiment, there is provided a compound of formula (1),

wherein Y In this embodiment, preferably R ₃ and R ₄ are selected from H or O-alkyl, and R ₅ is methyl.

According to one embodiment, there is provided a compound of formula (1), wherein Ri and R ₂ are selected from H, fluorine, chlorine, bromine, trifluoromethyUCi-β-allcyl, hydroxyl, Q _-6 alkoxy, or aralkyloxy.

According to one embodiment, there is provided a compound of formula (1), wherein Rj and R ₂ are selected from O-α or β-D-glucopyranosyl group, α or β-D- glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxylgroup may be esterified).

According to one embodiment, there is provided a compound of formula (IA):

wherein,

XA can be H, lower alkyl group, lower perfluoro alkyl group, O-α or β-D- glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxylgroup may be esterified); Ri _A and R _2A are independently can be selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl, Ci- ₆ -alkyl, hydroxyl, cyano, Ci _-6 alkoxy, C _3-7 cycloalkoxy, aryloxy, aralkyloxy, aryloxyalkyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified).

Pharmaceutically acceptable salts of the compounds of the formula (IA) are also contemplated. Likewise, pharmaceutically acceptable solvates, including hydrates, of the compounds of the formula (IA) are contemplated. It should be understood that the formula (IA) structurally encompasses all positional isomers, stereoisomers, including enantiomers and diastereomers that may be contemplated from the chemical structure of the genus described herein.

Also contemplated are prodrugs of the compounds of the formula (IA), including ester prodrugs.

Another preferred embodiment of the present invention is a compound of Formula (IB),

Formula (IB) wherein, XB can be H, lower alkyl group, O-α or β-D-glucopyranosyl group, α or β-D- glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified); Y _B can be

wherein,

Z _A can be (CH ₂ )n; n can be an integer 0-1;

Ring A _B and B _B are independently can be a phenyl; R _IB and R _2B independently can be selected from H, -Cl, -Br, -OMe, or CF ₃ ;

R _3B and R _4B are independently can be selected from H, alkyl, or O- alkyl;

R ₅ B can be alkyl. Pharmaceutically acceptable salts of the compounds of the formula (IB) are also contemplated. Likewise, pharmaceutically acceptable solvates, including hydrates, of the compounds of the formula (IB) are contemplated.

It should be understood that the formula (IB) structurally encompasses all positional isomers, stereoisomers, including enantiomers and diastereomers that may be contemplated from the chemical structure of the genus described herein.

Also contemplated are prodrugs of the compounds of the formula (IB), including ester prodrugs.

According to another embodiment, there is provided a pharmaceutical preparation, which comprises any one of the above tetrazole glycoside compounds or a pharmaceutically acceptable salt thereof or a hydrate thereof as an active ingredient.

According to another embodiment, there is provided such a pharmaceutical preparation which is an inhibitor of sodium-dependent glucose transporter 2 activity. According to another embodiment, there is provided such a pharmaceutical preparation which is a prophylactic or therapeutic agent for diabetes, diabetes- related diseases or diabetic complications.

Below are the representative compounds which are illustrative in nature only and are not intended to limit to the scope of the invention. 2-(acetoxymethyl)-6-(5-benzyl-2H-tetrazol-2-yl)tetrahydro-2H -pyran-3,4,5- triyl triacetate (Compound No. 1),

2-(5-benzyl-2H-tetrazol-2-yl)-6-(hydroxymethyl)tetrahydro -2H-pyran-3,4,5- triol (Compound No. 2),

2-(acetoxymethyl)-6-(5-(4-bromobenzyl)-2H-terrazol-2-yl)t etrahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 3),

2-(5-(4-bromobenzyl)-2H-tetrazol-2-yl)-6-(hydroxymethyl)t etrahydro-2H- pyran-3,4,5-triol (Compound No. 4),

2-(acetoxymethyl)-6-(5-(2,4-dichlorobenzyl)-2H-tetrazol-2 -yl)tetrahydro- 2H-pyran-3,4,5-triyl triacetate (Compound No. 5), 2-(5-(2,4-dichlorobenzyl)-2H-tetrazol-2-yl)-6-(hydroxymethyl )tetrahydro-

2H-pyran-3,4,5-triol (Compound No. 6),

2-(acetoxymethyl)-6-(5-(4-methoxybenzyl)-2H-tetrazol-2-yl )tetrahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 7), 2-(hydroxymethyl)-6-(5-(4-methoxybenzyl)-2H-tetrazol-2-yl)te trahydro-2H- ρyran-3 ,4,5-triol (Compound No. 8),

2-(acetoxymethyl)-6-(5-(3,4-dichlorobenzyl)-2H-tetrazol-2 -yl)tetrahydro- 2H-pyran-3,4,5-triyl triacetate (Compound No. 9), 2-(5-(3,4-dichlorobenzyl)-2H-tetrazol-2-yl)-6-(hydroxymethyl )tetrahydro-

2H-pyran-3,4,5-triol (Compound No. 10),

2-(acetoxymethyl)-6-(5-(4-(trifluoromethyl)benzyl)-2H-tet razol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 11),

2-(hydroxymethyl)-6-(5-(4-(trifluoromethyl)benzyl)-2H-tet razol-2- yl)tetrahydro-2H-pyran-3 ,4,5-triol (Compound No. 12),

2-(acetoxymethyl)-6-(5-(4-(benzyloxy)benzyl)-2H-tetrazol- 2-yl)tetrahydro- 2H-pyran-3,4,5-triyl triacetate (Compound No. 13),

2-(5-(4-(benzyloxy)benzyl)-2H-tetrazol-2-yl)-6-(hydroxyme thyl)tetrahydro- 2H-pyran-3,4,5-triol (Compound No. 14), 2-(acetoxymethyl)-6-(5-(4-hydroxybenzyl)-2H-tetrazol-2-yl)te trahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 15),

2-(5-(4-hydroxybenzyl)-2H-tetrazol-2-yl)-6-(hydroxymethyl )tetrahydro-2H- pyran-3 ,4,5-triol (Compound No. 16),

2-(acetoxymethyl)-6-(5-phenethyl-2H-tetrazol-2-yl)tetrahy dro-2H-pyran- 3,4,5-triyl triacetate (Compound No. 17),

2-(hydroxymethyl)-6-(5-phenethyl-2H-tetrazol-2-yl)tetrahy dro-2H-pyran- 3,4,5-triol (Compound No. 18),

2-(acetoxymethyl)-6-(5-(2-oxo-2-phenylethyl)-2H-tetrazol- 2-yl)tetrahydro- 2H-pyran-3,4,5-triyl triacetate (Compound No. 19), l-phenyl-2-(2-(3,4 _J 5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2- yl)-2H-tetrazol-5-yl)ethanone (Compound No. 20),

2-(acetoxymethyl)-6-(5-(2-(4-chlorophenoxy)ethyl)-2H-tetr azol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 21),

2-(5-(2-(4-chlorophenoxy)ethyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 22),

2-(acetoxymethyl)-6-(5-(4-methylbenzyl)-2H-tetrazol-2-yl) tetrahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 23),

2-(hydroxymethyl)-6-(5-(4-metliylbenzyl)-2H-tetrazol-2-yl )tetrahydro-2H- pyran-3,4,5-triol (Compound No. 24), 2-(acetoxymethyl)-6-(5-(4-ethylbenzyl)-2H-tetrazol-2-yl)tetr ahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 25),

2-(5-(4-ethylbenzyl)-2H-tetrazol-2-yl)-6-(hydroxymethyl)t etrahydro-2H- pyran-3,4,5-triol (Compound No. 26), 2-(acetoxymethyl)-6-(5-(2-methoxybenzyl)-2H-tetrazol-2-yl)te trahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 27),

2-(hydroxymethyl)-6-(5-(2-methoxybenzyl)-2H-tetrazol-2-yl )tetrahydro-2H- pyran-3,4,5-triol (Compound No. 28),

2-(acetoxymethyl)-6-(5-(3-methoxybenzyl)-2H-tetrazol-2-yl )tetrahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 29),

2-(hydroxymethyl)-6-(5-(3-methoxybenzyl)-2H-tetrazol-2-yl )tetrahydro-2H- pyran-3,4,5-triol (Compound No. 30),

2-(acetoxymethyl)-6-(5-(4-ethoxybenzyl)-2H-tetrazol-2-yl) tetrahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 31), 2-(5-(4-ethoxybenzyl)-2H-tetrazol-2-yl)-6-(hydroxymethyl)tet rahydro-2H- pyran-3,4,5-triol (Compound No. 32),

2-(acetoxymethyl)-4-hydroxy-6-(5-(4-isopropoxybenzyl)-2H- tetrazol-2- yl)tetrahydro-2H-pyran-3,5-diyl diacetate (Compound No. 33),

2-(hydroxymethyl)-6-(5-(4-isopropoxybenzyl)-2H-tetrazol-2 -yl)tetrahydro- 2H-pyran-3,4,5-triol (Compound No. 34), ethyl (3,4,5-trihydroxy-6-(5-(4-isopropoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-2-yl)methyl carbonate (Compound No. 35),

2-(acetoxymethyl)-6-(5-(4-benzylbenzyl)-2H-tetrazol-2-yl) tetrahydro-2H- pyran-3,4,5-triyl triacetate (Compound No. 36), 2-(5-(4-benzylbenzyl)-2H-tetrazol-2-yl)-6-(hydroxymetriyl)te trahydro-2H- pyran-3,4,5-triol (Compound No. 37),

2-(acetoxymethyl)-6-(4-((2-ethyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 38),

2-(4-((2-ethyl-2H-tetrazol-5-yl)methyl)phenoxy)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 39),

2-(acetoxymethyl)-6-(4-((2-metliyl-2H-tetrazol-5- yl)methyl)phenoxy)tetraliydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 40),

2-(hydroxymethyl)-6-(4-((2-methyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydiO-2H-pyran-3,4,5-triol (Compound No. 41), 2-(acetoxymethyl)-6-(5-(2-oxo-2-(l-phenylethylamino)ethyl)-2 H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 42),

N-(l-phenylethyl)-2-(2-(3,4,5-trihydroxy-6-(hydroxymethyl )tetrahydro-2H- pyran-2-yl)-2H-tetrazol-5-yl)acetamide (Compound No. 43), 2-(acetoxymethyl)-6-(5-(2-(l-(4-methoxyphenyl)ethylamino)-2- oxoetliyl)-

2H-tetrazol-2-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 44),

N-(l-(4-methoxyphenyl)ethyl)-2-(2-(3,4,5-trihydroxy-6-

(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-2H-tetrazol-5-yl )acetamide (Compound No. 45), or pharmaceutically acceptable salts, solvates, isomers, including hydrates and prodrugs of compounds 1-45 are also contemplated.

Also below are representative isomeric compounds which are exemplary in nature only and are not intended to limit to the scope of the invention.

/corner .4 o/2-(acetoxymethyl)-6-(5-benzyl-2H-tetrazol-2-yl)tetrahydro- 2H- pyran-3,4,5-triyl triacetate (Compound No. IA),

Isomer B o/2-(acetoxymethyl)-6-(5-benzyl-2H-tetrazol-2-yl)tetrahydro- 2H- pyran-3,4,5-triyl triacetate (Compound No. IB),

Isomer A o/2-(5-benzyl-2H-tetrazol-2-yl)-6-(hydroxymethyl)tetrahydro- 2H- pyran-3,4,5-triol (Compound No. 2A), Isomer B o/2-(5-benzyl-2H-tetrazol-2-yl)-6-(hydroxymethyl)tetrahydro- 2H- pyran-3,4,5-triol (Compound No. 2B),

Isomer A ø/2-(acetoxymethyl)-6-(5-(4-bromobenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 3A),

Isomer B o/2-(acetoxymethyl)-6-(5-(4-bromobenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 3B),

Isomer A o/2-(5-(4-bromobenzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 4A),

Isomer B o/2-(5-(4-bromobenzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 4B), Isomer A o/2-(acetoxymethyl)-6-(5-(2,4-dichlorobenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 5A),

J^ome7-5 o/2-(acetoxymethyl)-6-(5-(2,4-dichlorobenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 5B), Isomer A ø/2-(5-(2,4-dichlorobenzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3 _J 4,5-triol (Compound No. 6A),

Isomer B o/2-(5-(2,4-dichlorobenzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 6B), Isomer A o/ ^" 2-(acetoxymethyl)-6-(5-(4-methoxybenzyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 7A),

Isomer B o/2-(acetoxymethyl)-6-(5-(4-methoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 7B),

Isomer A o/2~(hydroxymethyl)-6-(5-(4-methoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 8A),

Isomer B o/ ^" 2-(hydroxymethyl)-6-(5-(4-methoxybenzyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 8B),

Isomer A <9/ ^" 2-(acetoxymethyl)-6-(5-(3,4-dichlorobenzyl)-2H-tetrazo l-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 9A), Isomer B o/2-(acetoxymethyl)-6-(5-(3,4-dichlorobenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 9B),

Isomer A o/2-(5-(3,4~dichlorobenzyl)-2H-tetrazol~2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 10A),

Isomer B o/2-(5-(3,4-dichlorobenzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 10B),

Isomer A o/2-(acetoxymethyl)-6-(5-(4-(trifluoromethyl)benzyl)-2H-tetr azol- 2-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. HA),

Isomer B o/2-(acetoxymethyl)-6-(5-(4-(trifluoromethyl)benzyl)-2H-tetr azol- 2-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 11B), Isomer A o/2-(hydroxymethyl)-6-(5-(4-(trifluoromethyl)benzyl)-2H-tetr azol-

2-yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 12A),

/5O7wer 5 o/2-(hydroxymethyl)-6-(5-(4-(trifluoromethyl)benzyl)-2H-tetr azol- 2-yl)tetrahydro-2H-pyran-3,4,5-triol (Compound Net. 12B),

/5θ7κer^ o/2-(acetoxymethyl)-6-(5-(4-(benzyloxy)benzyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 13A),

Λθ7«er5 o/2-(acetoxymethyl)-6-(5-(4-(benzyloxy)benzyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 13B),

Isomer A o/2-(5-(4-(benzyloxy)benzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-ρyran-3,4,5-triol (Compound No. 14A), Isomer B ø/2-(5-(4-(benzyloxy)benzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 14B),

Isomer A o/2-(acetoxymethyl)-6-(5-(4-hydroxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 15A), Isomer B o/ ^" 2-(acetoxymethyl)-6-(5-(4-hydroxybenzyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 15B),

Isomer A o/2~(5-(4-hydroxybenzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 16A),

Isomer B o/2-(5-(4-hydroxybenzyl)-2H-tetrazol-2-yl)-6- (hydroxymemyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 16B),

Isomer A o/2-(acetoxymethyl)-6-(5-phenethyl-2H-tetrazol-2-yl)tetrab.y dro- 2H-pyran~3 ,4,5-triyl triacetate (Compound No. 17A),

Isomer B <?/ ^' 2-(acetoxymethyl)-6-(5-phenethyl-2H-tetrazol-2-yl)tetr aliydro- 2H-pyran-3,4,5-triyl triacetate (Compound No. 17B), Isomer A o/2-(hydroxymethyl)-6-(5-phenethyl-2H-tetrazol-2-yl)tetrahyd ro-

2H-pyran-3,4,5-triol (Compound No. 18A),

Isomer B o/2-(hydroxymethyl)-6-(5-phenethyl-2H-tetrazol-2-yl)tetrahyd ro- 2H-pyran-3,4,5-triol (Compound No. 18B),

Isomer A o/2-(acetoxymethyl)-6-(5-(2~oxo-2-phenylethyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3 ,4,5-triyl triacetate (Compound No. 19A),

Isomer B o/2-(acetoxymethyl)-6-(5-(2-oxo-2-phenylethyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 19B),

Isomer A o/l-phenyl-2-(2-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydr o- 2H-pyran-2-yl)-2H-tetrazol-5-yl)ethanone (Compound No. 20A), Isomer B o/7-phenyl-2-(2-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydr o-

2H-pyran-2-yl)-2H-tetrazol-5-yl)ethanone (Compound No. 20B),

Isomer A o/2-(acetoxymethyl)-6-(5-(2-(4-chlorophenoxy)ethyl)-2H-tetra zol- 2-yl)tetrahydro-2H-pyran-3 ,4,5-triyl triacetate (Compound No. 21A),

/5 ⁱ omer-5 o/2-(acetoxymethyl)-6-(5-(2-(4-chlorophenoxy)ethyl)-2H-tetra zol- 2-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 21B),

/5O77ze/-^ o/2-(5-(2-(4-chlorophenoxy)ethyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 22A),

Ao/7zer5 o/2-(5-(2-(4-chlorophenoxy)ethyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-ρyran-3,4,5-triol (Compound No. 22B), Isomer A o/2-(acetoxymethyl)-6-(5-(4-methylbenzyl)-2H-tetrazol-2- yl)tetxahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 23A),

Λower 5 o/2-(acetoxymethyl)-6-(5-(4-methylbenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 23B), Isomer A o/2-(hydroxymethyl)-6-(5-(4-methylbenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 24A),

Isomer B o/2-(hydroxymethyl)-6-(5-(4-methylbenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 24B),

Isomer A o/2-(acetoxymethyl)-6-(5-(4-ethylbenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 25A),

Isomer B q/ ^" 2-(acetoxymethyl)-6-(5-(4-ethylbenzyl)-2H-tetrazol-2- yl)tetraliydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 25B),

Isomer A o/2-(5-(4-ethylbenzyl)-2H-tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 26A), Isomer B ø/2-(5-(4-emylbenzyl)-2H-tetrazol-2-yl)-6-

(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 26B),

Isomer A o/ ^' 2-(acetoxymethyl)-6-(5-(2-metlioxybenzyl)-2H-tetrazol- 2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 27A),

Isomer B o/2-(acetoxymethyl)-6-(5-(2-methoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 27B),

Isomer A o/2-(hydroxymethyl)-6-(5-(2-methoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 28A),

Isomer B q/ ^" 2-(hydroxymethyl)-6-(5-(2-methoxybenzyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 28B), Isomer A o/2-(acetoxymethyl)-6-(5-(3-methoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 29A),

Isomer B o/2-(acetoxymethyl)-6-(5-(3-methoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 29B),

Isomer A o/2-(hydroxymethyl)-6-(5-(3 -methoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 30A),

Isomer B o/ ^" 2-(hydroxymethyl)-6-(5-(3-methoxybenzyl)-2H-tetrazol-2 - yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 30B),

Λ<?7K(2r _J 4 o/2-(acetoxymethyl)-6-(5-(4-ethoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 31A), Isomer B o/2-(acetoxymethyl)-6-(5-(4-ethoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 31B),

Isomer A ø/2-(5-(4-ethoxybenzyl)-2H~tetrazol-2-yl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 32A), Isomer B ø/2-(5-(4-ethoxybenzyl)-2H-tetrazol-2-yl)-6-

(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 32B),

Isomer A of 2-(acetoxymethyl)-4-hydroxy-6-(5-(4-isopropoxybenzyl)-2H- tetrazol-2-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (Compound No. 33A),

Isomer B of 2-(acetoxymethyl)-4-hydroxy-6-(5-(4-isopropoxybenzyl)-2H- tetrazol-2-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (Compound No. 33B),

Isomer A of 2-(hydroxymethyl)~6~(5-(4-isopropoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 34A),

Isomer B of 2-(hydroxymethyl)-6-(5-(4-isopropoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 34B), Isomer A of ethyl (3,4,5-trihydroxy-6~(5-(4-isopropoxybenzyl)-2H-tetrazol-

2-yl)tetrahydro-2H-pyran-2-yl)methyl carbonate (Compound No. 35A),

Isomer B of ethyl (3,4,5-trihydroxy-6-(5-(4-isopropoxybenzyl)-2H-tetrazol- 2-yl)tetrahydro-2H-pyran-2-yl)methyl carbonate (Compound No. 35B),

Isomer A of 2-(acetoxymethyl)-6-(5-(4-benzylbenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 36A),

Isomer B of 2-(acetoxymethyl)-6-(5-(4-benzylbenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 36B),

Isomer A of 2-(5-(4-benzylbenzyl)-2H-tetrazol-2-yl)-6-

(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 37A), Isomer B of 2-(5-(4-benzylbenzyl)-2H-tetrazol-2-yl)-6-

(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 37B),

Isomer A of 2-(acetoxymethyl)-6-(4-((2-ethyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 38A),

Isomer B of 2-(acetoxymethyl)-6-(4-((2-ethyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 38B),

Isomer A of 2-(4-((2-ethyl-2H-tetrazol-5-yl)methyl)phenoxy)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 39A),

Isomer B of 2-(4-((2-ethyl-2H-tetrazol-5-yl)methyl)phenoxy)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 39B), Isomer A of 2-(acetoxymethyl)-6-(4-((2-methyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 40A),

Isomer B of 2-(acetoxymethyl)-6-(4-((2-methyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 40B), Isomer A of 2-(hydroxymethyl)-6-(4-((2-methyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H~pyran-3,4,5-trioI (Compound No. 41A),

Isomer B of 2-(hydroxymethyl)-6-(4-((2-methyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol (Compound No. 41B),

Isomer A of 2-(acetoxymethyl)-6-(5-(2-oxo-2-(l-phenylethylamino)ethyl)- 2H-tetrazol-2-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 42A),

Isomer B of 2-(acetoxymethyl)-6-(5-(2-oxo-2-(l-phenylethylammo)ethyl)- 2H-tetrazol-2-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 42B),

Isomer A of N-(l-phenylethyl)-2-(2-(3,4,5-trihydroxy-6-

(hydroxymetriyl)tetrahydro-2H-pyran-2-yl)-2H-tetrazol-5-y l)acetamide (Compound No. 43A),

Isomer B of N-(l-phenylethyl)-2-(2-(3,4,5-trihydroxy-6-

(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-2H-tetrazol-5-yl )acetamide (Compound No. 43B),

Isomer A of 2-(acetoxymethyl)-6-(5-(2-(l-(4-methoxyphenyl)ethylamino)-2- oxoethyl)-2H-tetrazol-2-yl)teti-ahydro-2H-pyran-3,4,5-triyl triacetate (Compound

No. 44A),

Isomer B of 2-(acetoxymethyl)-6-(5-(2-(l -(4-methoxyphenyl)ethylamino)-2- oxoethyl)-2H-tetrazol-2-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound No. 44B), Isomer A of N-(l-(4-methoxyphenyl)ethyl)-2-(2-(3,4,5-trihydroxy-6-

(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-2H-tetrazol-5-yl )acetamide (Compound No. 45A),

Isomer B of N-(l-(4-methoxyphenyl)ethyl)-2-(2-(3,4,5-trihydroxy-6- (hydroxymethyl)tetrahydro-2H-pyran-2-yl)-2H-tetrazol-5-yl)ac etamide (Compound No. 45B), or pharmaceutically acceptable salts, solvates, isomers, including hydrates and prodrugs of compounds 1A-45B are also contemplated.

The invention also provides a pharmaceutical composition that includes at least one compound of described herein and at least one pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Preferably, the pharmaceutical composition comprises a therapeutically effective amount of at least one compound described herein. The compound(s) present in the composition may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or may be diluted by a carrier, or enclosed within a carrier which may be in the foπn of a capsule, sachet, paper or other container.

The compounds and pharmaceutical compositions described herein are useful in the treatment of diseases, conditions and/or disorders mediated by SGLT2 inhibitors. The invention further provides a method of treating a disease, condition and/or disorder mediated by SGLT2 inhibitors in a subject in need thereof by administering to the subject one or more compounds described herein in the amount effective to cause inhibition of such receptor.

Also provided are SGLT2 activity ^' of compounds of the formula (1), (IA) or (IB), at two different concentrations like 10 μm and 3 μm in BBMVs and cell based assay.

Also provided herein are processes for preparing compounds described herein.

The invention provides a method for preventing, ameliorating or treating a SGLT2 mediated disease, disorder or syndrome in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of the invention. The invention further provides a method, wherein the

SGLT2 mediated disease, disorder or syndrome is diabetes, especially type I and type 11 diabetes, including complications of diabetes such as retinopathy, neuropathy, nephropathy and delayed wound healing, and related diseases such as insulin resistance and impaired glucose homeostasis (IGH), hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, obesity, hyperlipidemia including hypertriglyceridemia, Syndrome X, hypertension, atherosclerosis and related diseases, and for increasing high density lipid levels. The conditions, diseases, and maladies collectively referred to as "Syndrome X" (also known as Metabolic Syndrome).

The invention provides a method of treating diabetes in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to the invention. A number of assays have been published in the literature to assess the anti diabetes activity of the compounds. For example, in- vitro assays have been reported in Am J physiol Renal Physiol 286, Fl 27-Fl 33, 2004; Nature protocols, 2007, 2(6), 1356-59; EP Patent application EP 1813611 and J. Pharmacology and Experimental Therapeutics, 324, 985-991, 2008.

The invention provides a method of treating type I diabetes in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to the invention

The invention provides a method of treating type II diabetes in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to the invention.

The invention provides a process for the preparation of a compound of formula (I):

wherein,

X can be H, lower alkyl group, lower perfluoro alkyl group, aralkyl group, phenyl group, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxylgroup may be esterified);

Y can be

Ring A and B are independently can be selected from phenyl, naphthyl, heteroaryl, cycloalkyl or heterocyclyl which may contain 5 to 7 membered ring, which may contain 1 to 4 hetero atoms like N, O, S, SO or

SO ₂ in the ring; Z can be oxygen, methylene, (CH ₂ ) _n , dimethylmethylene, difluoromethylene, carbonyl, O-alkyl, S-alkyl, SO ₂ alkyl, -C(O)-NH-R ₁ R ₂ or Z may represent a bond between rings A and B; n can be an integer 0-3;

Y also can be , substituted or unsubstituted aryl group more particularly substituted or unsubstituted phenyl group, substituted or unsubstituted aryl-C(O)-, substituted or unsubstituted aryl- CH ₂ -, or substituted or unsubstituted aryloxy-CH2-, where in substituents are Ri and R ₂ ; Ri and R ₂ are independently can be selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl, Ci-β-alkyl, C _2-6 alkynyl, C _3- 6 cycloalkyl, C ₁ -C ₄ alkylcarbonyl, aryl carbonyl, heteroarylcarbonyl, amino carbonyl, Ci- ₄ -alkylaminocarbonyl, hydroxyl, cyano, Ci _-4 alkyl sulphonylamino, arylsulphonylamino, Ci- β alkoxy, C _3-7 cycloalkoxy, aryloxy, aralkyloxy, aryloxyalkyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified); R ₃ and R ₄ are independently can be selected from hydrogen, alkyl, halo, perfluoroalkyl, CN, OH, O-alkyl, O-cycloalkyl, phenyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D- glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified);

R ₅ can be alkyl or perfluoroalkyl; an analog thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable solvate thereof, a pharmaceutically acceptable hydrate thereof, an N- oxide thereof, a tautomer thereof, a regeoisomers thereof, a stereoisomer thereof, a prodrug thereof or a polymorph thereof, the process comprising the steps of: (a) reacting the cyano compounds of formula (1)

Y ^' ^CN 1 with the azide compounds of formula (2)

NaN ₃ 2 to form tetrazole compounds of formula (3)

(b) reacting the tetrazole compounds of formula (3) with the acylated sugar compounds of formula (4)

to form the acylated sugar compounds of formula (5)

5

Formula (1), when X is acylated glucopyranosyl _an( j

(c) hydrolysing the compounds of formula (5) to form the sugar compounds of formula (6)

6

Formula (1), when X is glucopyranosyl Alternatively, the invention provides a process for the preparation of a compound of formula (I): wherein,

X can be H, lower alkyl group, lower perfluoro alkyl group, aralkyl group, phenyl group, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxylgroup may be esterified);

Y can be

Ring A and B are independently can be selected from phenyl, naphthyl, heteroaryl, cycloalkyl or heterocyclyl which may contain 5 to 7 membered ring, which may contain 1 to 4 hetero atoms like N, O, S, SO or SO ₂ in the ring;

Z can be oxygen, methylene, (CH ₂ ) _n , dimethylmethylene, difluoromethylene, carbonyl, O-alkyl, S-alkyl, SO ₂ alkyl, -C(O)-NH-RiR ₂ or

Z may represent a bond between rings A and B; n can be an integer 0-3;

Y also can be , substituted or unsubstituted aryl group more particularly substituted or unsubstituted phenyl group, substituted or unsubstituted aryl-C(O)-, substituted or unsubstituted aryl-

CH ₂ -, or substituted or unsubstituted aryloxy-CH2-, where in substituents are Ri and R ₂ ;

R] and R ₂ are independently can be selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl, d-e-alkyl, C _2-6 alkynyl, C _3-6 cycloalkyl, Ci-C ₄ alkylcarbonyl, aryl carbonyl, heteroarylcarbonyl, amino carbonyl, C _1-4 -alkylaminocarbonyl, hydroxyl, cyano, C _1-4 alkyl sulphonylamino, arylsulphonylamino, C ₁ . 6 alkoxy, C _3-7 cycloalkoxy, aryloxy, aralkyloxy, aryloxyalkyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified);

R ₃ and R ₄ are independently can be selected from hydrogen, alkyl, halo, perfluoroalkyl, CN, OH, O-alkyl, O-cycloalkyl, phenyl,

O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D- glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified); R ₅ can be alkyl or perfluoroalkyl; an analog thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable solvate thereof, a pharmaceutically acceptable hydrate thereof, an N- oxide thereof, a tautomer thereof, a regeoisomers thereof, a stereoisomer thereof, a prodrug thereof or a polymorph thereof, the process comprising the steps of:

(a) reacting the amino compounds of formula (7)

with the cyano acetic acid compounds of formula (8)

HOOC^CN 8 to foπn the amido compounds of formula (9)

(b) reacting the amido compounds of formula (9) with the azide compounds of formula (2)

NaN3 to form the tetrazole compounds of formula (10)

(c) reacting the tetrazole compounds of formula (10) with the acylated sugar compounds of formula (4)

4 to form the acylated sugar compounds of formula (11)

11

Formula 1, when X is acylated glucopyraiiosyl JJi ₁ (J

(d) hydrolysing the acylated sugar compounds of formula (11) to form the sugar compounds of formula (12)

12

Formula 1, when X is I Q glucopyranosyl

Alternatively, the invention provides one more process for the preparation of a compound of formula (I):

wherein,

15 X can be H, lower allcyl group, lower perfluoro alkyl group, aralkyl group, phenyl group, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxylgroup may be esterified);

Y can be

Ring A and B are independently can be selected from phenyl, naphthyl, heteroaryl, cycloalkyl or heterocyclyl which may contain 5 to 7 membered ring, which may contain 1 to 4 hetero atoms like N, O, S, SO or SO ₂ in the ring;

Z can be oxygen, methylene, (CH ₂ ) _n , dimethylmethylene, difluoromethylene, carbonyl, O-alkyl, S-alkyl, SO ₂ alkyl, -C(O)-NH-RiR ₂ or

Z may represent a bond between rings A and B; n can be an integer 0-3;

Y also can be , substituted or unsubstituted aryl group more particularly substituted or unsubstituted phenyl group, substituted or unsubstituted aryl-C(O)-, substituted or unsubstituted aryl-

CH ₂ -, or substituted or unsubstituted aryloxy-CH2-, where in substiτuents are Ri and R ₂ ;

Ri and R ₂ are independently can be selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl, Ci- ₆ -alkyl, C _2-6 alkynyl, C3-6 cycloalkyl, Ci-C ₄ alkylcarbonyl, aryl carbonyl, heteroarylcarbonyl, amino carbonyl, Ci- ₄ -alkylaminocarbonyl, hydroxyl, cyano, Ci _-4 alkyl sulphonylamino, arylsulphonylamino, Ci- 6 alkoxy, C3 _-7 cycloalkoxy, aryloxy, aralkyloxy, aryloxyalkyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D-glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified); R ₃ and R ₄ are independently can be selected from hydrogen, alkyl, halo, perfluoroalkyl, CN, OH, O-alkyl, O-cycloalkyl, phenyl, O-α or β-D-glucopyranosyl group, α or β-D-glucopyranosyl group (of which one or more hydroxyl groups may be acylated) or β-D- glucuronyl group (of which one or more hydroxyl groups may be acylated and carboxyl group may be esterifled); R ₅ can be alkyl or perfluoroalkyl; an analog thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable solvate thereof, a pharmaceutically acceptable hydrate thereof, an N- oxide thereof, a tautomer thereof, a regeoisomers thereof, a stereoisomer thereof, a prodrug thereof or a polymorph thereof, the process comprising the steps of:

(a) reacting the cyano compounds of formula (13) (wherein, P is protecting group (benzyl or tertiary butyl))

with the azide compounds of formula (2)

NaN ₃ 2 to form the tetrazole compounds of formula (14)

(b) reacting the tetrazole compounds of formula (14) with the halo compounds of formula (15)

XBr 15 to form the compounds of formula (16)

(c) deprotecting the compounds of formula (16) to form the compounds of formula (17)

(d) reacting the compounds of formula (17) with the acylated sugar compounds of formula (4)

4 to form the acylated sugar compounds of formula (18)

18

Formula 1, when Y is phenyl substituted by acylated glucopyranosyl ajj(J

(e) hydrolysing the acylated sugar compounds of formula (18) to form the sugar compounds of formula (19)

Formula 1, when Y is phenyl substituted by glucopyranosyl The invention provides for use of a compound of the invention for the manufacture of a medicament for, for example, preventing, ameliorating or treating a SGLT2 mediated disease, disorder or syndrome in a subject in need thereof. The invention further provides for the use wherein the SGLT2 mediated disease, disorder or syndrome is diabetes, especially type I and type II diabetes, including complications of diabetes such as retinopathy, neuropathy, nephropathy and delayed wound healing, and related diseases such as insulin resistance and impaired glucose homeostasis (IGH), hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, obesity, hyperlipidemia including hypertriglyceridemia, Syndrome X, hypertension, atherosclerosis and related diseases, and for increasing high density lipid levels, and the conditions, diseases, and maladies collectively referred to as

"Syndrome X" (also known as Metabolic Syndrome). Detailed Description of the Invention

The invention provides tetrazole glycoside derivatives, which may be used as SGLT2 inhibitors and processes for the synthesis of these compounds. Pharmaceutically acceptable salts, pharmaceutically acceptable solvates, positional isomers, enantiomers, diastereomers, polymorphs of these compounds that may have the same type of activity are also provided. Pharmaceutical compositions containing the described compounds together with pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of diseases, condition and/or disorders mediated by SGLT2 inhibitors are further provided. The following definitions apply to the terms as used herein:

The terms "halogen" or "halo" includes fluorine, chlorine, bromine, or iodine.

The term "alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to eight carbon atoms, and which is attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n- pentyl, and 1,1-dimethylethyl (t-butyl).

The term "alkenyl" refers to an aliphatic hydrocarbon group containing a carbon-carbon double bond and which may be a straight or branched chain having from 2 to about 10 carbon atoms, e.g., ethenyl, 1-propenyl, 2-propenyl (allyl), iso- propenyl, 2-methyl- 1-propenyl, 1-butenyl, and 2-butenyl.

The term "haloalkyl" is used to denote a group comprised of an alkyl group substituted with halogen atom, where alkyl group is as defined above and halogen is used to denote fluorine, chlorine, bromine or iodine, an example of such group is trifluoromethyl, difluoromethyl.

The term "acyl group" is used to denote a linear or branched aliphatic acyl group (preferably a C _2-6 alkanoyl group) or an aromatic acyl group, which contains 2 to 10 carbon atoms. Examples include an acetyl group, a propionyl group, a pivaloyl group, a butyryl group, an isobutyryl group, a valeryl group and a benzoyl group, with an acetyl group being preferred.

The term "alkoxy group" is used to denote a linear or branched alkoxy group containing 1 to 6 carbon atoms. Preferred are C _1-4 alkoxy groups including a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group and a tert-butoxy group. The term "cycloalkyl" denotes a non-aromatic mono or multicyclic ring system of from 3 to about 12 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples of multicyclic cycloalkyl groups include, but are not limited to, perhydronapththyl, adamantyl and norbornyl groups, bridged cyclic groups and spirobicyclic groups, e.g., spiro (4,4) non-2-yl.

The term "cycloalkylalkyl" refers to a cyclic ring-containing radical having from 3 to about 8 carbon atoms directly attached to an alkyl group. The cycloalkylalkyl group may be attached to the main structure at any carbon atom in the alkyl group that results in the creation of a stable structure. Non-limiting examples of such groups include cyclopropylmethyl, cyclobutylethyl, and cyclopentylethyl.

The term "cycloalkenyl" refers to a cyclic ring-containing radical having from 3 to about 8 carbon atoms with at least one carbon-carbon double bond, such as cyclopropenyl, cyclobutenyl, and cyclopentenyl. The term "aryl" refers to an aromatic radical having from 6 to 14 carbon atoms such as phenyl, naphthyl, tetrahydronapthyl, indanyl, and biphenyl.

The term "arylalkyl" refers to an aryl group as defined above directly bonded to an alkyl group as defined above, e.g., -CH ₂ C ₆ Hs and -C ₂ H ₅ C ₆ Hs.

The terms "heterocyclyl" and "heterocyclic ring" refer to a stable 3- to 15- membered ring radical which consists of carbon atoms and from one to five heteroatoms selected from nitrogen, phosphorus, oxygen and sulfur. For purposes of this invention, the heterocyclic ring radical may be a monocyclic, bicyclic or tricyclic ring system, which may include fused, bridged or spiro ring systems, and the nitrogen, phosphorus, carbon, oxygen or sulfur atoms in the heterocyclic ring radical may be optionally oxidized to various oxidation states. In addition, the nitrogen atom may be optionally quaternized; and the ring radical may be partially or fully saturated (i.e., heterocyclic or heteroaryl). Examples of such heterocyclic ring radicals include, but are not limited to, azetidinyl, acridinyl, benzodioxolyl, benzodioxinyl benzodioxanyl, benzofuranyl, carbazolyl, cinnolinyl, dioxolanyl, indolizinyl, naphthyridinyl, perhydroazepinyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pyridyl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrazoyl, imidazolyl, tetrahydroisouinolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolinyl, oxazolidinyl, triazolyl, indanyl, isoxazolyl, isoxasolidinyl, morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, octahydroindolyl, octahydroisoindolyl, quinolyl, isoquinolyl, decahydroisoquinolyl, benzimidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl, benzooxazolyl, furyl, tetrahydrofurtyl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, dioxaphospholanyl, oxadiazolyl, chromanyl, and isochromanyl. The heterocyclic ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. The term "heterocyclylalkyl" refers to a heterocyclic ring radical directly bonded to an alkyl group. The heterocyclylalkyl radical may be attached to the main structure at any carbon atom in the alkyl group that results in the creation of a stable structure.

The term "heteroaryl" refers to an aromatic heterocyclic ring radical. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure.

The term "heteroarylalkyl" refers to a heteroaryl ring radical directly bonded to an alkyl group. The heteroarylalkyl radical may be attached to the main structure at any carbon atom in the alkyl group that results in the creation of a stable structure. Unless otherwise specified, the term "substituted" as used herein refers to, for example, substitution with any one or any combination of the following substituents: hydroxy, halogen, carboxyl, cyano, nitro, oxo (=0), thio (=S), substituted or unsubstituted alkyl, haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic ring, substituted or unsubstiuted guanidine,

-COOR ^X , -C(O)R ^X , -C(S)R ^X , -C(O)NR ^x R ^y , -C(O)ONR ^x R ^y , -NR ^x C0NR ^y R ^z , - N(R ^x )SOR ^y , -N(R ^x )SO ₂ R ^y , -(=N-N(R ^x )R ^y ), -NR ^x C(O)OR ^y , -NR ^x R ^y , -NR ^x C(O)R ^y , - NR ^x C(S)R ^y , -NR ^x C(S)NR ^y R ^z , -SONR ^x R ^y , -SO ₂ NR ^x R ^y , -OR ^X , -OR ^x C(O)NR ^y R ^z , - OR ^x C(O)OR ^y , -OC(O)R ^X , -OC(O)NR ^x R ^y , -R ^x NR ^y C(O)R ^z , -R ^x OR ^y , -R ^x C(O)OR ^y , - R ^x C(O)NR ^y R ^z , -R ^x C(O)R ^y , -R ^x OC(O)R ^y , -SR ^X , -SOR ^X , -SO ₂ R ^X , and -ONO ₂ , wherein R ^x , R ^y and R ^z are independently selected from hydrogen, substituted or unsubstituted alkyl, haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, or substituted or unsubstituted heterocyclic ring. The substituents in the aforementioned "substituted" groups cannot be further substituted. For example, when the substituent on "substituted alkyl" is "substituted aryl", the substituent on "substituted aryl" cannot be "substituted alkenyl".

The term "prodrug" means a compound that is transformed in vivo to yield, for example, a compound of Formula (1), Formula (IA), or Formula (IB) or a pharmaceutically acceptable salt, hydrate or solvate of the compound. The transformation may occur by various mechanisms, such as through hydrolysis in blood. A discussion of the use of prodrugs is provided by T. Higuchi and W. Stella, "Pro-drugs as Novel Delivery Systems," Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987.

The term "treating" or "treatment" of a state, disease, disorder or condition includes, for example:

(1) preventing or delaying the appearance of clinical symptoms of the state, disease, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disease, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disease, disorder or condition;

(2) inhibiting the state, disease, disorder or condition, e.g., arresting or reducing the development of the state, disease, disorder or condition or at least one clinical or subclinical symptom thereof; or

(3) relieving the state, disease, disorder or condition, e.g., causing regression of the state, disease, disorder or condition or at least one of its clinical or subclinical symptoms. The benefit to a subject receiving treatment is either statistically significant or at least perceptible to the subject or to the physician.

The term "subject" includes, for example, mammals (especially humans) and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non-domestic animals (such as wildlife).

A "therapeutically effective amount" means, for example, the amount of a compound that, when administered to a subject for treating a state, disease, disorder or condition, is sufficient to effect such treatment. The "therapeutically effective amount" will vary depending on the compound, the state, disease, disorder or condition and its severity and the age, weight, physical condition and responsiveness of the subject receiving treatment.

The term "diabetes" encompasses, for example, type I diabetes, type II diabetes, and other types of diabetes with specific etiology.

The term "diabetes-related diseases" includes, for example, adiposis, hyperinsulinemia, abnormal carbohydrate metabolism, hyperlipidernia, hypercholesterolemia, hypertriglyceridemia, abnormal lipid metabolism, hypertension, congestive heart failure, edema, hyperuricemia and gout.

The term "diabetic complications" can be classified into acute complications and chronic complications. The term "acute complications" includes, for example, hyperglycemia (e.g., ketoacidosis), infections (e.g., skin, soft tissue, biliary system, respiratory system and urinary tract infections), etc.

The term "chronic complications" includes, for example, microangiopathy (e.g., nephropathy, retinopathy), arteriosclerosis (e.g., atherosclerosis, heart infarction, brain infarction, or lower extremity arterial occlusion), neuropathy (e.g., sensory nerves, motor nerves, or autonomic nerves), foot gangrene, etc. Major complications are diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.

The compound of invention may form salts. Non-limiting examples of pharmaceutically acceptable salts forming part of the invention include salts derived from inorganic bases salts of organic bases salts of chiral bases, salts of natural amino acids and salts of non-natural amino acids. Certain compounds of invention are capable of existing in stereoisomeric forms (e.g. diastereomers and enantiomers) or as positional isomers. With respect to the overall compounds described by the Formula (I), the invention extends to these stereoisomer^ forms and to mixtures thereof. To the extent prior art teaches synthesis or separation of particular stereoisomers, the different stereo isomeric forms of the invention may be separated from one another by the method known in the art, or a given isomer may be obtained by stereospecific or asymmetric synthesis. Tautomeric forms and mixtures of compounds described herein are also contemplated.

All stereoisomers of the compounds of this invention are contemplated, either admixture or substantially pure form or in pure form. The compounds of present invention have asymmetric centers at any of the carbon atoms including any one of the R substituents. Thus the compounds of formula (1), formula (IA), or formula (IB) can exist in racemic, enantiomeric or diasteriomeric forms or in mixtures thereof. The process for preparation can utilize racemates, enantiomers, or diastereomers as starting materials. When diastereomeric or enantiomeric products are prepared, they can be separated by conventional methods for example, chromatographic or fractional crystallization.

Pharmaceutically acceptable solvates includes, for example, hydrates and other solvents of crystallization (such as alcohols). The compounds of the present invention may form solvates with low molecular weight solvents by methods known in the art. Phannaceutical Compositions

The phannaceutical compositions provided in the invention include at least one compound described herein and at least one pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Preferably, the contemplated pharmaceutical compositions include a compound(s) described herein in an amount sufficient to inhibit SGLT2 in a subject.

The subjects contemplated include, for example, a living cell and a mammal, including human mammal. The compound of the present invention may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or be diluted by a carrier, or enclosed within a carrier which can be in the form of a capsule, sachet, paper or other container.

Examples of suitable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone.

The carrier or diluent may include a sustained release material, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax.

The pharmaceutical composition may also include one or more pharmaceutically acceptable auxiliary agents, wetting agents, emulsifying agents, suspending agents, preserving agents, salts for influencing osmotic pressure, buffers, sweetening agents, flavoring agents, colorants, or any combination of the foregoing. The pharmaceutical composition of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the subject by employing procedures known in the art.

The pharmaceutical compositions described herein may be prepared, e.g., as described in Remington: The Science and Practice of Pharmacy. 20 ^th Ed., 2003 (Lippincott Williams & Wilkins). For example, the active compound can be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of an ampoule, capsule, sachet, paper, or other container. When the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material that acts as a vehicle, excipient, or medium for the active compound. The active compound can be adsorbed on a granular solid container, for example, in a sachet.

The pharmaceutical compositions may be, for example, capsules, tablets, aerosols, solutions, suspensions or products for topical application.

The route of administration may be any route which effectively transports the active compound to the appropriate or desired site of action. Suitable routes of administration include, but are not limited to, oral, nasal, pulmonary, buccal, subdermal, intradermal, transdermal, parenteral, rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic (such as with an ophthalmic solution) or topical (such as with a topical ointment). The oral route is preferred. Solid oral formulations include, but are not limited to, tablets, capsules (soft or hard gelatin), dragees (containing the active ingredient in powder or pellet form), troches and lozenges. Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Preferable carriers for tablets, dragees, or capsules include lactose, cornstarch, and/or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed.

A typical tablet that may be prepared by conventional tabletting techniques may contain: (1) Core: Active compound (as free compound or salt thereof), 250 mg colloidal silicon dioxide (Aerosil®), 1.5 mg microcrystalline cellulose (Avicel®), 70 mg modified cellulose gum (Ac-Di-Sol®), and 7.5 mg magnesium stearate; (2) Coating: HPMC, approx. 9 mg Mywacett 9-40 T and approx. 0.9 mg acylated monoglyceride.

Liquid formulations include, but are not limited to, syrups, emulsions, soft gelatin and sterile injectable liquids, such as aqueous or non-aqueous liquid suspensions or solutions.

For parenteral application, particularly suitable are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil. Methods of Treatment

The present invention provides compounds and pharmaceutical formulations thereof that are useful in the treatment of diseases, conditions and/or disorders mediated by SGLT2 inhibitors. The connection between therapeutic effect and inhibition of SGLT2 is illustrated. For example in PCT publication Nos. WO 01//016147, WO 02/08306, or WO 03/020737; J. Clin. Invest. Vol. 79, pp. 1510-

1515 (1987); J.Clin. Invest, Vol. 93, pp. 397-404 (1994); Diabetes; 57, 1723-1729, 2008 and references cited therein, all of which are incorporated herein by reference in their entirety and for the purpose stated.

The present invention further provides a method of treating a disease, condition and/or disorder mediated by SGLT2 inhibitors in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound or a pharmaceutical composition of the present invention.

Diseases, conditions, and/or disorders that are mediated by SGLT2 inhibitors include, but are not limited to, diabetes, especially type I and type 11 diabetes, including complications of diabetes such as retinopathy, neuropathy, nephropathy and delayed wound healing, and related diseases such as insulin resistance and impaired glucose homeostasis (IGH), hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, obesity, hyperlipidemia including hypertriglyceridemia, Syndrome X, hypertension, atherosclerosis and related diseases, and for increasing high density lipid levels. The conditions, diseases, and maladies collectively referred to as "Syndrome X" (also known as Metabolic Syndrome) are detailed in Johannsson, J. CHn. Endrocrinol. Metab. , 82, 727-34 (1997) incorporated herein by reference. The compounds of the present invention can obtain more advantageous effects than additive effects in the prevention or treatment of the above diseases when using suitably in combination with the above drugs. Also, the administration dose can be decreased in comparison with administration of either drug alone, or adverse effects of co administrated drugs other than SGLT2 inhibitors can be avoided or declined.

Methods of Preparation

The compounds described herein may be prepared by techniques known in the art. In addition, the compounds described herein may be prepared by following the reaction sequence as depicted in Scheme 1-3. Further, in the following schemes, where specific bases, acids, reagents, solvents, coupling agents, etc., are mentioned, it is understood that other bases, acids, reagents, solvents, coupling agents etc., known in the art may also be used and are therefore included within the present invention. Variations in reaction conditions, for example, temperature and/or duration of the reaction, which may be used as known in the art, are also within the scope of the present invention. All the stereo isomers of the compounds in these schemes, unless otherwise specified, are also encompassed within the scope of this invention.

Scheme 1

X is

6

Formula (1), when X is glucopyranosyl

The compounds of Formula (1) (wherein, X and Y are same as defined above) can be prepared by the above procedure as described in Scheme 1. The nitrile compounds of formula 1 can be treated with sodium azide compounds of formula 2 to give the tetrazole compounds of formula 3 (as described in J. Organic chemistry, 2001, 66, 7945-7950) in presence of metal halides such as, zinc bromide or the like in the solvents for example, isopropyl alcohol in water, or the like. The tetrazole compounds of formula 3 can be reacted with the acylated-bromo sugar compounds of formula 4 (as described in Organic Synthesis Collective volume 3, page 11, 1955) to give the acylated sugar compounds of formula 5 in presence of a base such as, potassium or cesium carbonate or the like in the solvents such as, for example, acetonitrile, chloroform or the like. The acylated sugar compounds of formula 5 can be hydrolyzed to give the sugar compounds of formula 6 in the presence of hydrolyzing agents such as, for example methanolic ammonia, or the like. Produgs of compounds of formula 1 can be prepared by reacting the haloformates in the presence of a base like triethyl amines.

Sclleme-2

12 11

Formula 1, when X is Formula 1, when X is glucopyranosyl acylated glucopyranosyl The compounds of Formula (1) (wherein, X, Y, R ₃ , R ₄ , and R ₅ are same as defined above) also can be prepared by the above procedure as described in Scheme 2. The nitrile amine compounds of formula 7 can be treated with the acidic-nitrile compounds of formula 8 to give the amide-nitrile compounds of foπnula 9 in presence of coupling agents such as l-(3-dimethyl aminopropyl)-3 -ethyl carbodiimide hydrochloride, 1-hydroxy-benzotriazole or the like in the solvents such as dimethyl formamide or the like. The amide-nitrile compounds of formula 9 can be treated with sodium azide compounds of formula 2 to give the tetrazole compounds of formula 10 (as described in J. Organic chemistry, 2001, 66, 7945-7950) in presence of metal halides such as, zinc bromide or the like in the solvents for example, isopropyl alcohol in water, or the like. The tetrazole compounds of formula

10 can be reacted with the acylated-bromo sugar compounds of formula 4 (as described in Organic Synthesis Collective volume 3, page 11, 1955) to give the acylated sugar compounds of formula 11 in presence of a base such as, potassium or cesium carbonate or the like in the solvents such as, for example, acetonitrile, chloroform or the like. The acylated sugar compounds of formula 11 can be hydro lyzed to give the sugar compounds of formula 12 in the presence of hydrolyzing agents such as, for example methanolic ammonia, or the like. Produgs of compounds of formula 1 can be prepared by reacting the haloformates in the presence of a base like triethyl amines.

substituted by glucopyranosyl substituted by aoylated glucopyranosyl

The compounds of Formula (1) (wherein, P is protecting group (benzyl or tertiary butyl), X, and Y are same as defined above) also can be prepared by the above procedure as described in Scheme 3. The nitrile compounds of formula 13 can be reacted with sodium azide compounds of formula 2 to give the tetrazole compounds of formula 14 (as described in J. Organic chemistry, 2001, 66, 7945- 7950) in presence of metal halides such as, zinc bromide or the like in the solvents for example, isopropyl alcohol in water, or the like. The tetrazole compounds of formula 14 can be reacted with the bromo compounds of formula 15 to give the compounds of formula 16 in presence of base such as, potassium or cesium carbonate or the like in the solvents such as, for example, acetonitrile, chloroform or the like. The compounds of formula 16 can be deprotected in presence of deprotecting agents such as palladium on carbon or the like to give the hydroxy compounds of formula 17. The hydroxy compounds of formula 17 can be reacted with the acylated-bromo sugar compounds of formula 4 (as described in Organic Synthesis Collective volume 3, page 11, 1955) to give the acylated sugar compounds of formula 18 in presence of a base such as, potassium or cesium carbonate or the like in the solvents such as, for example, acetonitrile, chloroform or the like. The acylated sugar compounds of formula 18 can be hydrolyzed to give the sugar compounds of formula 19 in presence oh hydrolyzing agents such as, for example methanolic ammonia, or the like. Produgs of compounds of formula 1 can be prepared by reacting the haloformates in the presence of a base like triethyl amines.

It is known in the literature that the addition of sodium azide to nitriles to give tetrazoles may processed either a two step mechanism or a concepted 2+3 cyclo addition giving a scope of forming either of regeoisomers or a mixture of regeoisomers. These isomers are separable by chromatography either at this stage or at the later stage.

Experimental The present invention is further illustrated by the following examples, which are not to be construed in any way as imposing limitations upon the scope of this disclosure, but rather are intended to be illustrative only. On the contrary, it is to be clearly understood that resort may be had to various other embodiments, modifications, and equivalents thereof which, after reading the description herein, may suggest themselves to one of ordinary skill in the art without departing from the spirit of the present invention. Thus, the skilled artisan will appreciate how the experiments and Examples may be further implemented as disclosed by variously altering the following examples, substituents, reagents, or conditions.

Examples Example 1: Preparation of (6S)-2-facetoxymethyl)-6-f5-benzyl-2H-tetrazol-2- yl)tetrahvdro-2H-pyran-3 ,4,5-triyl triacetate:

Step 1: Synthesis of 5-benzyl-2H-tetrazole

Sodium azide (about 3 g, 4.7 equivalent) was added to a mixture of phenylacetonitrile (about 1 g, 1 equivalent) and Zinc Bromide (about 1.5 g, 0.7 equivalent) in isopropyl alcohol/water (10 ml/30 ml). Contents were refiuxed at about 80° C for about 48 hours under vigorous stirring. Completion of the reaction was monitored by TLC. The Reaction mixture was cooled to room temperature and the P ^H was adjusted to 1.0 with diluted HCl and stirred for about 10 minutes then extracted with ethyl acetate (3x20 ml). The combined organic layers were washed with NaHCO ₃ solution and brine solution, dried over magnesium sulphate (MgSO ₄ ) and concentrated in vacuo to afford the title compound as a white solid. Yield: 85%;

¹ H NMR (300 MHz, CDCl ₃ ): δ, 4.29 (s, 5H), 5.88 (s, 2H), 7.25-7.34 (m, 5H, Ar-H), 16.20 (Jars, IH, NH); Mass [M+Naf: 183(100%).

Step 2: Preparation of 2-(acetoxymethyl)-6-(5-benzyl-2H-tetrazol-2-yl)tetrahydro- 2H-pyran-3, 4, 5-triyl triacetate:

Anhydrous K ₂ CO ₃ (about 1.28 g, 3 equivalent) was added to acetonitrile (10 ml) followed by 5-Benzyl-2H-Tetrazole (stepl, about 0.5 g, 1 equivalent), after stirring the contents for about five minutes, tetra acetyl bromoglucose (about 1.65 g, 1.3 equivalent),) was added and the mixture was refluxed at about 80°C for about 5 hours. Completion of the reaction was monitored by TLC. The reaction mixture was filtered and washed with CH ₃ CN and filtrate was poured into ice water while stirring then extracted with ethyl acetate (3x10 ml) and washed with water and 12% brine solution. Solvent was removed under reduced pressure to give the isomers of title compound (Isomer A and Isomer B) then the isomers of mixture were separated by silica gel column chromatography using 12% EtOAc: Hexane to afford the final isomers.

Isomer A: Mp: 159.5-161 ⁰ C; IR: 1741, 1754, 1377, 1254, 1227 cm ⁴ ; ¹ H NMR: 1.78 (s, 3H), 2.05 (s, 3H), 2.10 (s, 6H), 4.0 (m, IH), 4.17 (d, IH), 4.25-4.31 (d, H & s, 2H), 5.30 (t, IH), 5.40 (t, IH), 5.92 (t, IH), 6.02 (d, IH); 7.2-7.4 (m, 5H); HPLC:

97.389%; Mass (M+Na)=513.

Isomer B: Mp: 152.1-154 ⁰ C; IR: 1751, 1254, 1377, 1227 cm ^"1 ; ¹ H NMR: 1.82 (s, 3H), 2.0-2.18 (s, 9H), 3.65 (m, IH), 3.98 (dd, IH), 4.2 (dd, IH), 4.4 (dd, 2H), 5.2 (t, IH), 5.3 (t, IH), 5.5-5.62 (m, 2H), 7.2-7.4 (m, 5H); Mass (M+Na)=513; HPLC: 95.8%. Example 2: Σ-fS-benzyl-lH-tetrazol-Σ-ylVό-diydroxymethyDtetrahvdro^H -pyran- 3.4.5-triol:

2-(acetoxymethyl)-6-(5-benzyl-2H-tetrazol-2-yl)tetrahydro-2H -pyran-3,4,5- triyl triacetate (Example 1, about 1 g) was added in portion wise to methonolic ammonia solution (about 20 ml), and stirred for about 3 hours at room temperature. The reaction mixture was allowed for concentration under reduced pressure. The residue was taken in to ethyl acetate and washed with saturated brine solution (2x30 ml), dried over sodium sulphate, filtered and concentrated in vacuo to afford the title compound. Yield: 55%.

Isomer A: MP: 135.5-142.5 ⁰ C; IR: 3371, 3439 cm ⁴ ; ¹ H NMR: 3.6-3.7 (m, 3H), 3.75-3.95 (m, 3H), 4.2-4.3 (m, 3H), 4.6 (brs, IH), 4.7 (brs, IH), 5.05 (bra, IH), 5.75 (brs, IH), 7.2-7.4 (m, 5H); Mass (M+Na)=345; HPLC: 97.1%. Isomer B: IR: 3410, 1459, 1069 cm ^"1 ; ¹ H NMR: 3.3 (S, IH), 3.4 (s, 3H), 3.6 (s, IH),

3.9 (s, 1,H), 4.4 (s, 2H), 4.6 (s, IH), 5.2 (s, IH), 5.25 (s, IH), 5.55 (s, IH), 5.65 (s, IH), 7.2-7.4 (m, 5H); Mass (M+Na)=345; HPLC: 97.3%.

Similarly, the following compounds have been prepared by above procedure with corresponding starting materials:

Example 3 : 2-(acetoxymethyl)-6-(5-f4-bromobenzyl)-2H-tetrazol-2-yl)tetr ahydro- 2H-pyran-3 A5-triyl triacetate:

Isomer A: Mp: 154.2-156.0 ⁰ C; IR: 1746, 1372, 1248 cm ^"1 ; ¹ H NMR: 1.9 (s, 3H), 2.0-

2.18 (s, 9H), 4.05 (brs, IH), 4.08-4.18 (m, 4H), 5.25 (t, IH), 5.40 (t, IH), 5.82 (t, IH), 6.02 (d, IH), 7.2 (d, 2H), 7.43 (d, 2H); Mass (M+Na)=593; HPLC: 99.984%. Isomer B: Mp:161.6-163.5°C; IR: 1750, 1376, 1253, 1226 cm ^"1 ; ¹ H NMR: 1.92 (s, 3H), 2.0-2.18 (3 s, 9H), 3.9 (s, IH), 4.04 (s, IH), 4.2-4.4 (m, 3H), 5.2 (t, IH), 5.17 (t, IH), 5.22 (t, IH), 5.70 (d, IH), 7.19 (d, 2H), 7.45 (d, 2H); Mass (M+Na)=593; HPLC: 96.95%.

Example 4: 2-(5-(4-bromobenzyl)-2H-tetrazol-2-ylV6-fhvdroxymethγl')tet rahvdro- 2H-υyran-3.4,5-triol:

Isomer A: Mp: 92.8-101.2 ⁰ C; IR: 3436, 3352 cm ⁴ ; ¹ H NMR: 3.2 (s, IH), 3.6-3.68 (m, 3H), 3.8 (m, IH), 3.9 (m, IH), 4.22 (s, 3H), 4.59 (s, IH), 4.62 (s, IH), 5.0 (s, IH), 5.8 (d, IH), 7.22 (d, 2H), 7.42 (d, 2H); Mass (M+Na)=423; HPLC: 98.62%. Isomer B: IR: 3392, 1662, 1071cm ^"1 ; ¹ H NMR: 3.3-3.37 (m, 2H), 3.44-3.75 (m, 4H), 3.78-3.82 (m, 2H), 4.18 (t, IH), 4.4 (s, 2H), 4.6 (s, IH), 5.59 (d, IH), 7.24 (d, 2H), 7.45 (d, 2H); Mass (M+Na)=423; HPLC: 95.04%.

Example 5j 2-(acetoxymethyl)-6-(5-f2,4-dicmorobenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate:

Isomer A: Mp: 96.2-97.2 ⁰ C; IR: 1739, 1746, 1753, 1372, 1249 Cm ⁴ ; ¹ H NMR: 1.9 (s, 3H), 2.0-2.07 (s , 9H), 4.0 (s, IH), 4.2 (d, IH), 4.3 (m, IH), 4.4 (s, 2H), 5.25 (m, IH), 5.4 (m, IH), 5.8 (m, IH), 6.05 (d, IH), 7.25 (d, 2H), 7.4 (s, IH); Mass (M+Na)=581; HPLC: 97.48%.

Isomer B: Mp: 171.2-172.8 ⁰ C; IR: 1738, 1750, 1376, 1225 cm ^"1 ; ¹ H NMR: 1.94 (s, 3H), 2.0-2.18 (s , 9H), 3.95 (s, IH), 4.1 (d, IH), 4.2 (d, IH), 4.5 (q, 2H), 5.25 (t, IH), 5.4 (t, IH), 5.62 (t, IH), 5.8 (d, IH), 7.24 (m, 2H), 7.45 (s,lH); Mass (M+Na)=581; HPLC: 99.09%.

Example 6: 2-f5-C2.4-dichlorobenzyl)-2H-tetrazol-2-ylV6- divdroxymethvDtetrahvdro-2H-pyran-3,4.,5-triol:

Isomer A: Mp: 88.2-98.2 ⁰ C; IR: 3351, 1474, 1199, 1073 cm ^"1 ; ¹ H NMR: 3.05 (s, IH), 3.2 (m, IH), 3.38-3.54 (m, 2H), 3.68 (m, IH), 3.84 (m, IH), 4.38 (s, 2H), 4.64 (s, IH), 5.15-5.3 (dd, 2H), 5.45 (s, IH), 5.8 (d, IH), 7.4-7.5 (dd, 2H), 7.65 (s, IH); Mass (M+Na)=413; HPLC: 99.819%.

Isomer B: IR: 3368, 1664, 1066 cm ⁴ ; ¹ H NMR: 3.3 (s, 2H), 3.5 (m, 3H), 3.65 (m, IH), 3.8 (m, IH), 4.1 (m, IH), 4.5 (m, 4H), 5.6 (m, IH), 7.3 (m, 2H), 7.5 (s, IH); Mass (M+Na)=413; HPLC: 93.54%.

Example 7 : 2-facetoxymethyl)-6-f 5-(4-methoxybenzylV2H-tetrazol-2-yl)tetrahydro- 2H-pyran-3.4.5-triyl triacetate:

Isomer A: Mp: 130.2-133.2 ⁰ C; IR: 1739, 1752, 1373, 1226 cm ^"1 ; ¹ H NMR: 1.78 (s, 3H), 2.0-2.12 (3 s, 9H), 3.8 (s, 3H), 4.0 (m, IH), 4.2 (m, 3H), 4.28 (m, IH), 5.25 (t, IH), 5.4 (t, IH), 5.86 (t, IH), 6.02 (d, IH), 6.84 (d, 2H), 7.22 (d, 2H); Mass (M+Na)=543; HPLC: 98.959%.

Isomer B: Mp: 163.9-166 ⁰ C; IR: 1748, 1369, 1226 cm ^"1 ; ¹ H NMR: 1.65 (s, 3H), 2.0- 2.1 (3 s, 9H), 3.7 (m, IH), 3.8 (s, 3H), 4.02 (d, IH), 4.2 (dd, IH), 4.35 (m, 2H), 5.2 (t, IH), 5.3 (t, IH), 5.5-5.62 (m, 2H), 6.9 (d, 2H), 7.18 (d, 2H); Mass (M+Na)=543; HPLC: 94.4%.

Example 2-πivdroxymethyl)-6-(5-f4-methoxybenzyl)-2H-tetrazol-2- yl ^" )tetrahvdro-2H-pyran-3,4.5-triol:

Isomer A: Mp: 92.1-98.8 ⁰ C; IR: 3371, 1515, 1252, 1672 cm ^'1 ; ¹ H NMR: 3.2 (s, IH), 3.42 (s, IH), 3.6-3.8 (m, 6H), 3.98 (s, 3H), 4.22 (s, IH), 4.98 (s, IH), 5.32 (s, IH) ₃ 5.7 (s, IH), 6.7 (d, 2H), 7.1 (d, 2H); Mass (M+Na)=375; HPLC: 99.83%. Isomer B: Mp: 92.1-98.8 ⁰ C; IR: 3358, 1663, 1250, 1070 cm ^"1 ; ¹ H NMR: 3.3-3.4 (m, 5H), 3.5 (m, 2H), 3.7 (m, IH), 3.8 (m, 4H), 4.18 (m, IH), 4.38 (m, 2H), 5.52 (d,

IH), 6.9 (d, 2H), 7.24 (d, 2H); Mass (M+Na)=375; HPLC: 99.43%.

Example 9j 2-facetoxymethyl)-6-(5-f3,4-dichlorobenzyl)-2H-tetrazol-2- yl)tetrahγdro-2H-pyran-3 ,4.5-triyl triacetate:

Isomer A: Mp: 126.1-127.5 ⁰ C; IR: 1737, 1753, 1376, 1225 cm ^'1 ; ¹ H NMR: 1.6 (s, 3H), 2.0-2.12 (s , 9H), 4.05 (m, IH), 4.38-4.7 (m, 4H), 5.3 (t, IH), 5.4 (t, IH), 5.85 (t, IH), 6.05 (d, IH), 7.15 (d, IH), 7.4 (dd, 2H); Mass (M+Na)=581; HPLC: 97.1%. Isomer B: Mp: 150.5-151.9 ⁰ C; IR: 1747, 1759, 1369, 1223 cm ^'1 ; ¹ H NMR: 1.83 (s,

3H), 2.01-2.12 (s, 9H), 3.85 (m, IH), 4.1 (d, IH), 4.3-4.4 (m, 3H), 5.25 (t, IH), 5.4 (m, 2H), 5.8 (d, IH), 7.18 (d, IH), 7.45 (dd, 2H); Mass (M+Na)=581; HPLC: 98.58%.

Example 10: 2-f5-f3.4-dichlorobenzyl)-2H-tetrazol-2-ylV6-

(hydroxymethyl)tetøhvdro-2H-pyran-3A5-triol:

Isomer A: Mp: 150.5-151.9 ⁰ C; IR: 3351, 1369, 1073cm ^'1 ; ¹ H NMR: 3.2 (s, IH), 3.5 (t, IH), 3.65 (m, 2H), 3.85 (m, 2H), 4.25 (m, 3H), 4.55 (d, 2H), 4.85 (d, IH), 5.8 (d, IH), 7.2 (dd, IH), 7.4 (m, 2H); Mass (M+Na)=413; HPLC: 98.29%.

Isomer B: IR: 3357, 1665, 1071cm ^'1 ; ¹ H NMR: 3.25 (m, 3H), 3.5-3.7 (m, 4H), 3.660-3.9 (m, 2H), 4.14 (t, IH), 4.42 (s, 2H), 5.6 (d, IH), 7.25 (dd, IH), 7.43-7.59 (m, 2H); Mass (M+Na)=413; HPLC: 86.85%. Example 11 : 2-(acetoxymethylV6-(5-('4-( ^' trifluoromethyl')benzylV2H-tetrazol-2- yl)tetrahydro-2H-pyran-3 ,4,5-triyl triacetate:

Isomer A: Mp: 168.2-169.8 ⁰ C; IR: 1746, 1328, 1227 cm ^"1 ; ¹ H NMR: 1.78 (s, 3H), 2.0-2.12 (s, 9H), 4.0 (m, IH), 4.12-4.3 (m, 2H), 4.34 (s, 2H), 5.22-5.38 (dd, IH),

5.42 (d, IH), 5.83 (t, IH), 6.04 (d, IH), 7.44 (d, 2H), 7.58 (d, 2H); Mass (M+Na)=581; HPLC: 99.40%.

Isomer B: Mp: 155.4-156.8 ⁰ C; IR: 1748, 1227 cm ⁴ ; ¹ H NMR: 1.84 (s, 3H), 2.0-2.16 (s, 9H), 3.86 (dd, IH), 4.06 (dd,lH), 4.3 (dd, IH), 4.46 (s, 2H), 5.2 (m, IH), 5.38 (t, 2H), 5.8 (t, IH), 7.42 (d, 2H), 7.64 (d, 2H); Mass (M+Na)=581; HPLC: 97.87%.

Example 12: 2-rhydroxymethylV6-(5-f4-ftrifluoromethyl)benzylV2H-tetrazol -2- vDtetrahvdro-2H-ϋyran-3,4.5-triol:

Isomer A: Mp: 104.8-112 ⁰ C; IR: 3431, 3352, 1335, 1119 cm ⁴ ; ¹ H NMR: 3.5-3.78

(m, 4H), 3.8-3.95 (m, 2H), 4.18-4.35 (m, IH), 4.38 (s, 2H), 4.62 (d, 3H), 5.0 (d, IH), 5.8 (d, IH), 7.4-7.62 (m, 4H); Mass (M+Na)=413; HPLC: 99.73%. Isomer B: IR: 3364, 1664, 1328, 1067 cm ^"1 ; ¹ H NMR: 3.34 (m, 4H), 3.42-3.64 (m, 3H), 3.66-3.86 (m, 2H), 4.14 (t, IH), 4.54 (s, 2H), 5.6 (d, IH), 7.53 (d, 2H), 7.66 (d, 2H); Mass (M+Na)=413; HPLC: 96.48%.

Example 13 : 2-facetoxymethyl)-6-(5-( ^' 4-(benzyloxy)benzyl')-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4.5-triyl triacetate:

Isomer A: Mp: 150.1-151.8 ⁰ C; IR: 1748, 1370, 1226 cm ^"1 ; ¹ H NMR: 1.77 (s, 3H),

2.0-2.16 (s, 9H), 3.78-4.06 (m, IH), 4.2 (s, 3H), 4.3 (dd, IH), 5.02 (s, 2H), 5.32 (dd, IH), 5.42 (d, IH), 5.86 (t, IH), 6.03 (d, IH), 6.92 (d, 2H), 7.19-7.28 (m, 3H), 7.32- 7.44 (m, 4H); Mass (M+Na)=619; HPLC:98.83%.

Isomer B: Mp: 141.5-144.4 ⁰ C; IR: 1738, 1750, 1376, 1225 cm ^"1 ; ¹ H NMR: 1.8 (s, 3H), 2.0-2.16 (s, 9H), 3.66-3.76 (m, IH), 4.01 (dd, IH), 4.22 (dd, IH), 4.32 (s, 2H), 5.06 (s, 2H), 5.14-5.36 (m, 2H), 5.5-5.62 (m, 2H), 6.96 (d, 2H), 7.17 (d, 2H), 7.3- 7.48 (m, 5H); Mass (M+Na)=619; HPLC: 98.88%.

Example 14: 2-f5-f4-fbenzyloχy)benzylV2H-tetrazol-2-yl)-6- fhvdroxymethyl)tetrahvdro-2H-ρyran-3,4,5-triol:

Isomer A: Mp: 101.5-108.2 ⁰ C; IR: 3404, 1513, 1250 cm ^"1 ; ¹ H NMR: 3.2-3.32 (m, IH), 3.56-3.76 (m, 3H), 3.78-3.96 (m, 2H), 4.2 (s, 3H), 4.42 (s, 2H), 4.66 (d, IH), 5.04 (s, 2H), 5.78 (d, IH), 6.92 (d, IH), 7.22-7.32 (m, 3H), 7.34-7.46 (m, 4H); Mass (M+Na)=451; HPLC: 99.95%.

Isomer B: IR: 3351, 1662, 1510, 1244 cm ^"1 ; ¹ H NMR: 3.3-3.38 (m, 4H), 3.42-3.56 (m, 3H), 3.6-3.82 (m, 2H), 4.08-4.18 (m, IH), 4.36 (d, 2H), 5.08 (s, 2H), 5.5 (d, IH), 6.92-7.02 (m, 2H), 7.18-7.28 (m, 2H), 7.3-7.48 (m, 5H); Mass (M+Na)=451; HPLC: 99.25%.

Example L5j 2-(acetoxymemylV6-(5-f4-hvdroxybenzviy2H-tetrazol-2- yl)tetrahγdro-2H-pyran-3 A5-triyl triacetate:

Isomer A: Mp: 143.5-145.5 ⁰ C; IR: 3457, 1749, 1228 cm ⁴ ; ¹ H NMR: 1.75 (s, 3H), 1.95-2.15 (2s, 9H), 4.0 (m, IH), 4.2 (s, 3H), 4.25 (m, IH), 5.2 (brs, IH), 5.3 (t, IH), 5.4 (t, IH), 5.85 (t, IH), 6.05 (d, IH), 6.8 (d, 2H), 7.2 (d, 2H); Mass (M+Na)=529; HPLC: 97.27%.

Isomer B: Mp: 191.3-192.5 ⁰ C; IR: 3344, 1751, 1224 cm ^"1 ; ¹ H NMR: 1.85 (s, 3H), 2.0-2.1 (s, 9H), 3.7 (m, IH), 4.0 (d, IH), 4.2 (dd, 2H), 4.35 (d, 2H), 5.2 (t, IH), 5.3 (t, IH), 5.55 (d, 2H), 5.65 (s, IH), 6.8 (d, 2H), 7.2 (d, 2H); Mass (M+Na)=529; HPLC: 96.5%.

Example 16j 2-(5-(4-hvdroxybenzyl)-2H-tetrazol-2-ylV6- fliydroxymetlivDtetrahvdro-2H-pyran-3,4,5-triol:

Isomer A: IR: 3400, 2927, 1517, 1238 cm ⁴ ; ¹ H NMR: 3.35 (s, 2H), 3.5 (m, IH), 3.6-3.8 (m, 3H), 3.9 (d, IH), 4.15 (m, 3H), 4.65 (brs, IH), 5.9 (d, IH), 6.75 (d, 2H), 7.15 (d, 2H); Mass (M+l)=339; HPLC: 92.2%. Isomer B: Mp: 209-211 ⁰ C; IR: 3439, 3371, 1495, 1074 cm ^'1 ; ¹ H NMR: 3.3 (m, 2H),

3.4 (m, 2H), 3.6 (m, IH), 3.9 (m, IH), 4.25 (s, 2H), 4.65 (m, IH), 5.2 (d, IH), 5.3 (d, IH), 6.7 (d, 2H), 7.1 (d, 2H), 9.4 (s, IH); Mass (M+Na)=361; HPLC: 92.2%.

Example 17 : 2-( acetoxymethyl)-6~f 5-phenethyl-2H-tetrazol-2-yl)tetrahydro-2H- pyran-3 A5-triyl triacetate:

Isomer A: Mp: 92.0-99.9 ⁰ C; IR: 1748, 1370, 1222 cm ^'1 ; ¹ H NMR: 2.0-2.15 (4 s, 12H), 3.1 (t, 2H), 3.25 (t, 2H), 4.05 (dd, IH), 4.2 (dd, J=12.6Hz, IH), 4.3 (dd, J=12.75Hz, IH), 5.3 (t, J= 9.9, 9.6Hz, IH), 5.4 (t, J=9.3Hz, IH), 6.85 (t, J=9.6,9.3 Hz, IH), 6.05 (d, J= 9.3 Hz, IH), 7.2-7.35 (m,5H); HPLC: 99.6%; Mass

(M+Na)=527.

Isomer B: Mp: 125.4-131.1 ⁰ C; IR: 1763, 1745 , 1242, 1221cm ^{"1; 1} H NMR: 1.9 (s, 3H), 2.0 (s, 3H), 2.05 (2s, 6H), 3.25 (m, 4H), 3.9 (dd, dd, J=I 0.5, 4.8, 4.5Hz, IH), 4.15 (dd, J=12.6Hz, IH), 4.25 (dd, J=12.75 Hz, IH), 5.25 (t, J= 9.9, 9.6Hz, IH), 5.35 (t, J= 9.3Hz, IH), 5.6 (t, J=9.6, 9Hz, IH), 5.65 (d, J=9.6Hz, IH), 7.2-7.4 (m,

5H); HPLC: 99.3%; Mass (M+Na)=527.

Example 18: 2-giydroxymethyl)-6-('5-phenethyl-2H-tetrazol-2-yl)tetrahvdr o-2H- ϋyran-3A5-triol:

Isomer A: IR: 3353, 1663 cm ⁴ ; ¹ H NMR: 3.05 (m, 2H), 3.15 (m, 2H), 3.25 (m, IH), 3.5 (m, 2H), 3.7 (m, IH), 3.9 (m, IH), 4.7 (brs, IH), 5.2-5.4 (2 brs, 2H), 5.5 (bis, IH), 5.8 (d, J=15.5Hz, IH), 6.7 (brs, IH), 7.15-7.35 (m,5H); Mass (M+Na)=359; HPLC: 93.8%.

Isomer B: MP: 161.8-171.6 ⁰ C; IR: 3424, 3390, 3233 cm ^"1 ; ¹ R NMR: 3.05 (m, 2H), 3,25 (m, 2H), 3.45 (m, 2H), 3.55 (m, IH), 3.7(m, IH), 3.85 (m, IH), 4.7 (m, IH), 5.25 (d, J=9 Hz, IH), 5.3 (d, J=9Hz, IH), 5.55 (d, J=9.5Hz, IH), 5.65 (d, J=15 Hz, IH), 6.7 (brs, IH), 7.2-7.4 (m, 5H); Mass (M+Na)=359.

Example 19 : 2-(acetoxymetriyl)-6-r5-r2-oxo-2-phenylethylV2H-tetrazol-2- yl)tetrahydro-2H-pyran-3 A5-triyl triacetate:

Isomer A: Mp: 134.3-138.4 ⁰ C; IR: 1746, 1693, 1223 cm ^'1 ; ¹ H NMR: 1.85 (s, 3H) ₅ 2.0-2.15 (3s, 9H), 4.0-4.1 (m, IH), 4.2 (m, IH), 4.3 (m, IH), 4.65 (s, 2H), 5.3 (m, IH), 5.4 (m, IH), 5.85 (m, IH), 6.1 (m, IH), 7.15 (t, J=13,12Hz, 2H), 7.6 (t, /=13,12.5 Hz, IH), 8.0 (d, J=12 Hz, IH); HPLC: 99.7%; Mass (M+Na)=541. Isomer B: Mp: 95.6-115.3 ⁰ C; IR: 1756, 1683, 1369, 1228 cm ^"1 ; ¹ H NMR: 1.95-2.1 (4 s, 12H), 3.45 (m, IH), 4.95 (m, IH), 4.2 (m, IH), 4.35 (m, IH), 5.2 (m, IH), 5.3 (m, IH), 5.7 (m, IH), 5.95 (d, IH, 15.5 Hz), 7.5 (m, 2H), 7.65 (m, 2H);HPLC: 90.3%; Mass (M+Na): 518.

Example 20: l-phenyl-2-( ^' 2-( ^' 3,4.5-trihvdroxy-6-('hvdroxymethvntetrahvdro-2H- Oyran-2-yl)-2H-tetrazol-5-yl)ethanone:

Isomer A: IR: 3358, 1664 cm ^"1 ; ¹ H NMR: 3.15 (m, 2H), 3.55 (m, IH), 3.7 (m, IH), 3.9 (m, IH), 4.75 (m, IH), 4.85 (d, J=8.5Hz, IH), 5.25 (d, J=9Hz, IH), 5.35 (d, J=9Hz, IH), 5.55 (d, J=IOHz ₅ IH), 5.9 (d, J=15.5Hz, IH), 6.7 (brs, IH), 7.3 (brs, IH), 7.6 (t, J=13,12Hz, 2H), 7.7 (t, /=13,12.5 Hz, IH), 8.1 (d, J=12Hz, 2H); HPLC:

74.6%; Mass (M+Na): 373.

Isomer B: IR: 3358, 1664 cm ^"1 ; ¹ H NMR: 3.05 (m, 2H), 3.1-3.3 (m, 3H), 3.5 (m, IH), 3.7 (m, IH), 3.9 (m, IH), 4.7 (brs, IH), 5.3 (brs, IH), 5.55 (brs, IH), 5.8 (d, J=15.5Hz, IH), 6.7 (brs, IH), 7.15-7.40 (m, 5H); HPLC: 48+42 (isomers, 0.3 RT difference)% ; Mass (M+ 1 )=351 (molecular ion peak) .

Example 21 : 2-(acetoxymethyl)-6-(5-(2-(4-chlorophenoxy)ethyl)-2H-tetrazo l-2- yl)tetrahydro-2H-pyran-3 ,4,5-triyl triacetate:

Isomer A: Mp: 142.7-143.8 ⁰ C; IR: 1754, 1246, 1228 cm ^"1 ; ¹ H NMR: 1.76 (S, 3H),

2.0-.1 (3S, 9H), 3.4 (t, J= 6.6 Hz, 2H), 4.05 (m, H), 19 (m, IH), 4.3 (d, J=4.8 Hz, IH), 4.35 (t, J=6.9, 6.6 Hz, 2H), 5.3 (t, J=9.6, 9.3 Hz, IH), 5.4 (t, J=9.6, 9.3Hz, IH), 4.85 (t, J= 9.9, 9.6 Hz, IH), 6.05 (d, J=9.3Hz, IH), 6.83 (d, J= 9Hz, 2H), 7.23 (d, J= 9Hz, 2H); HPLC: 99.7%; Mass : M+Na: 577. Isomer B: Mp: 108.9-113.9 ⁰ C; IR: 1743.7, 1225, 1224 cm ^"1 ; ¹ H NMR: 1.84 (S, 3H),

2.05 -2.09 (3S, 9H), 3.47-3.52 (m, 2H), 4.0 (m, IH), 4.2-4.25 (m, 2H), 4.42-4.46 (m, 2H), 5.3 (t, IH), 5.45 (t, J= 9.6, 9.3 Hz, IH), 5.7 (t, J=9.6, 9.3 Hz, IH), 6.0 (d, J=9.6 Hz, IH), 6.85 (d, J= 9Hz, 2H), 7.25 (d, J=9 Hz, 2H); Mass: M+Na: 577; HPLC: 91.2%.

Example 22j 2-f5-f2-f4-chloroOhenoxy^ethyD-2H-tetrazol-2-yr)-6- divdroxymethyl')tetrahvdro-2H-pyran-3,4,5-triol:

Isomer A: IR: 3338, 1493, 1248 cm ⁴ ; ¹ H NMR: 3.25 (m, IH), 3.7 (m, IH), 3.65- 3.85 (m, 3H), 3.9 (m, IH), 4.4 (m, 4H), 4.6 (t, J=5.7, 5.4 Hz, IH), 5.25 (d, J=5.4 Hz, IH), 5.35 (d, J=5.4, Hz, IH), 5.55 (d, J=6 Hz, IH), 5.85 (d, J=9.3 Hz, IH), 6.9 (d, J=8.7Hz, 2H), 7.3 (d, J=8.7 Hz, 2H); Mass (M+Na): 409; HPLC: 95.6%. Isomer B: IR: 3403, 1243 cm ^'1 ; ¹ H NMR: 3.65 (m, 2H), 3.85 (m, IH), 4.4 (m, 2H), 4.5 (m, 2H), 4.7 (m, IH), 4.8 (m, IH), 4.9 (m, 3H), 5.2 (d, J=5.1 Hz, IH), 5.3 (d, J=5.1Hz, IH), 5.6 (d, J=5.7 Hz, IH), 5.7 (d, J=9 Hz, IH), 7.0 (d, J=9 Hz, 2H), 7.3 (d, J=9Hz, 2H); Mass (M+Na) =409; HPLC: 90.3%.

Example 23 : 2-(acetoxymethyl)-6-f 5-(4-methylbenzylV2H-tetrazol-2-yl)tetraliydro- 2H-υyran-3 A5-triyl triacetate:

Isomer A: Mp: 131.8-137 ⁰ C; IR: 1749, 1736, 1257, 1227 cm ^"1 ; ¹ H NMR: 1.75 (s, 3H), 2.0-2.1 (3s, 9H), 2.3 (s, 3H), 4.0 (m, IH), 4.15 (dd, /=14 Hz, IH), 4.22 (s, 2H), 4.29 (dd, J=16Hz, IH), 5.3 (t, J=16.5, 16 Hz, IH), 5.4 (t, J=16, 15.5Hz, IH), 5.88 (t, J=15.5 Hz, IH), 6.05 (d, J=16 Hz, IH), 7.12 (d, J=13Hz, 2H), 7.2 (d, J=13.5 Hz, 2H); Mass (M+Na)= 527; HPLC: 99.7%.

Isomer B: Mp: 144.2-149.9 ⁰ C; IR: 1742, 1369, 1255, 1226 cm ^"1 ; ¹ H NMR: 1.82 (s, 3H), 2.0-2.1 (3s, 9H), 2.35 (s, 3H), 3.7 (dd, J=13.8 Hz, IH), 3.98 (dd, J=21 Hz, IH), 4.2 (dd, J=21 Hz, IH), 4.35 (s, 2H), 5.2 (t, J=16 Hz, IH), 5.28 (m, IH), 5.58 (m, 2H), 7.1-7.2 (m,4H); Mass (M+Na)= 527; HPLC: 98.7%.

Example 24: 2-(hvdroxymethyl)-6-( ^' 5-(4-methylbenzylV2H-tetrazol-2-yl')tetrahvdro- 2H-pyran-3.4.5-triol:

Isomer A: IR: 3357, 1663, 1395, 1352 cm- ¹ ; ¹ H NMR: 2.25 (s, 3H), 3.2 (m, IH), 3.68 (m, IH), 3.88 (m, IH), 4.2 (s, 2H), 4.7 (m, IH), 5.25 (brs, IH), 5.35 (brs, IH), 5.5 (d, J= 8Hz, IH), 5.82 (d, 7=15 Hz, IH), 6.7 (brs, 2H), 7.15 (d, J=13Hz, 2H), 7.2 (d, J=13.5Hz, 2H), 7.35 (brs, 2H); Mass (M+Na)=359; HPLC: 83.8%. Isomer B: IR: 3351, 1660, 1393, 1257 cm ^{"1; 1} H NMR: 2.25 (s, 3H), 3.6 (m, IH), 3.85 (m, IH), 4.35 (s, 2H), 4.62 (m, IH), 5.22 (d, J=8.5 Hz, IH), 5.32 (d, J=9 Hz, IH), 5.58 (d, J=9 Hz, IH), 5.65 (d, J=15 Hz, IH), 6.72 (brs, 2H), 7.12 (d, J=13 Hz, 2H), 7.2 (d, J=I 3 Hz, 2H), 7.3 (brs, 2H); Mass (M+Na)= 359; HPLC: 78.85%.

Example 25 : 2-racetoxymethyl)-6-(5-(4-ethylbenzyl)-2H-tetrazol-2-yl)tetr ahydro- 2H-pyran-3.4.5-triyl triacetate:

Isomer A: Mp: 139.8-149.4 ⁰ C; IR: 1748, 1251, 1228 , 1215 cm ^"1 ; ¹ H NMR: 1.2 (t, 7=7.8, 7.5 Hz, 3H), 2.0-2.15 (4s, 12H), 2.62 (m, 2H), 4.02 (m, IH), 4.15 (m, IH), 4.24 (s, 2H), 5.15 (m, IH), 5.3 (t, 7=10.2, 9.9 Hz, IH), 5.4 (t, 7=9.6, 9.3 Hz, IH), 5.85 (t, 7=9.3 Hz, IH), 6.05 (d, J=9.6 Hz, IH), 7.05-7.25 (m, 4H); Mass (M+Na)=541; HPLC: 95.7%.

Isomer B: Mp: 162.5-164.1 ⁰ C; IR: 1743, 1252, 1225 cm ^"1 ; ¹ H NMR: 1.2 (t, J= Hz, 3H), 1.82 (s, 3H), 2.0-2.1 (3s, 9H), 2.65 (q, J= 7.5Hz, 2H), 3.68 (m, IH), 3.96 (m, IH), 4.22 (m, IH), 4.35 (m, 2H), 5.2 (t, 7=9.9, 9.3 Hz, IH), 5.28 (t, 7=9.3, 8.7 Hz, IH), 5.55 (t, 7=9.3, 8.4 Hz, IH), 5.6 (d, J=9 Hz, IH), 7.19 (m, 4H, Ar-H); Mass (M+Na)=5541; HPLC: 99.21%.

Example 26: 2-f5-f4-ethylbenzyl)-2H-tetrazol-2-yl)-6-rhydroxymethγl)tet rahydro- 2H-pyran-3.4.5-triol:

Isomer A: Mp: ⁰ C; IR: 3325, 1667, 1264 cm- ¹ ; ¹ H NMR: 1.15 (t, J=7.8, 7.5 Hz, 3H), 2.55 (m, 2H), 3.2 (m, IH), 3.52 (m, IH), 3.69 (m, IH), 3.85 (m, IH), 4.2 (s, 2H), 4.7(m, IH), 5.2-5.35 (2brs, 2H), 5.52 (m, IH), 5.82 (d, J=9Hz, IH), 6.72 (brs, 2H), 7.17 (d, J=9 Hz, 2H), 7.72 (brs, 2H); Mass (M+Na)=373; HPLC: 92.9%. Isomer B: IR: 3401, 1664, 1619, 1449, 1094, 1065 cm ⁴ ; ¹ H NMR: 1.15 (t, J=7.8, 7.5Hz, 3H), 2.57 (m, 2H), 3.3 (m, IH), 3.85 (m, IH), 4.35 (s, 2H), 4.62 (m, IH), 5.2 (d, J=5.4 Hz, IH, OH), 5.3 (d, J=5.3Hz, IH, OH), 5.6 (d, J=5.7 Hz, IH), 5.67 (d, J=9 Hz, IH), 7.14 (d, J=7.8 Hz, 2H), 7.23 (d, J=8.1 Hz, 2H); Mass (M+Na)=373; HPLC: 95.23%.

Example 2_7j 2-facetoxyniethylV6-f5-(2-methoxybenzyl)-2H-tetrazol-2- vDtetrahydro-2H-pyran-3 A5-triyl triacetate:

Isomer A: Mp: 107.6-112.2 ⁰ C; IR: 1747,1369, 1223 cm ^"1 ; ¹ H NMR: 1.76 (s, 3H), 2.1 (2s, 9H), 3.8 (s, 3H, OCH ₃ ), 4.0 (m, IH), 4.18 (m, IH), 4.25-4.35 (m, 3H), 5.3 (t, J=9.6Hz, IH), 5.38 (t, J=9.3 Hz, IH) ₅ 5.88 (t, J=9.3 Hz, IH), 6.05 (d, J=9.6 Hz, IH), 6.85-6.95 (m, 2H), 7.15-7.3 (m, 2H); Mass (M+Na)=543; HPLC: 99.28%. Isomer B: Mp: 124.1-130.6 ⁰ C; ¹ H NMR: 1.75 (s, 3H), 2.05 (3s, 9H), 3.7 (m, IH), 3.8 (s, 3H, OCH ₃ ), 4.0 (m, IH), 4.37 (m, 2H), 5.2-5.4 (m, 2H), 5.67-5.8 (m, 2H), 6.95 (t, J=8.1, 7.2 Hz, 2H), 7.2-7.35 (m, 2H), Mass (M+Na)=544; HPLC: 98.77%.

Example 28 : 2-( hvdroxymethylV 6-f 5-f 2-methoxyberizylV2H-tetrazol-2- yl)tetrahvdrc-2H-pyran-3A5-triol:

Isomer A: Mp: 78.9-94.7 ⁰ C; IR: 3416, 3299 cm ^"1 ; ¹ H NMR (300MHz, CDCl ₃ ): 3.7(m, IH), 3.52-3.72 (m, 3H), 3.8 (s, 3H, OCH ₃ ), 3.87 (m, IH), 4.1 (m, IH), 4.25 (s, 2H), 5.82 (d, J=9.3 Hz, IH), 6.88-7.0 (m, 2H), 7.15-7.3 (m, 2H); Mass (M+Na)=375; HPLC: 97.5%.

Isomer B: IR: 3424 cm ^"1 ; ¹ H NMR: 3.45 (m, IH), 3.45-3.5 (m, 2H), 3.65 (dd, IH), 3.75 (s, IH), 4.15 (m, IH), 4.35 (s, 2H), 5.52 (d, J=9 Hz, IH), 6.9-7.0 (m, 2H), 7.2- 7.35 (m, 2H); Mass (M+Na)=375; HPLC: 98.2%.

Example 29j 2-(acetoxymemylV6-(5-f3-methoxybenzylV2H-tetrazol-2- yl)tetrahydro-2H-pyran-3 ,4.5-triyl triacetate:

Isomer A: Mp: 153.6-156-6 ⁰ C; IR: cm ^"1 ; ¹ H NMR: 1.76 ( s, 3H), 2.0-2.14 (3 S, 9H), 3.8 (s, 3H, OCH ₃ ), 4.02 (m, IH), 4.19 (m, 2H), 4.25 (s, 2H), 4.3 (m, IH), 5.3 (t, J=9.9, IH), 5.4 (t, J=9.3, IH), 5.85 (t, J=9.3, IH), 6.05 (d, J=9.6, IH), 6.78-6.95 (m, 3H), 7.25 (t, J=8.1, 7.8 Hz, IH); HPLC: 98.67%; Mass (M+Na)=543. Isomer B: Mp: 153.3-154-6 ⁰ C; ¹ H NMR: 1.74 ( s, 3H), 1.98-2.1 (3 S, 9H), 3.77 (s, 3H, OCH ₃ ), 4.0 (m, IH), 4.12-4.28 (m, 2H), 4.42 (m, 2H), 5.23 (t, J=9.9, 9.3Hz, IH), 5.5 (t, J=9.6, 9.3Hz, IH), 5.65 (t, J=9.3Hz, IH), 6.24 (d, J=9 Hz, IH), 6.87 (m, 3H), 7.25 (t, J=8.7, 7.5 Hz, IH); HPLC: 98.29%; Mass (M+Na)=543.

Example 3Jh 2-(hydroxymethyl)-6-(5-( ^' 3-methoxybenzylV2H-tetrazol-2- yl)tetrahvdro-2H-pyran-3.4.5-triol:

[ _α -j Isomer A: ¹ H NMR: 3.48 (t, IH), 3.55 (m, 2H), 3.62 (m, IH), 3.7 (t, IH), 3.75 (s, 3H, OCH ₃ ), 3.85 (m, IH) ₅ 4.1 (m, IH), 4.22 (s, 2H), 5.8 (d, J=9 Hz, IH), 6.8 (m, 3H), 7.2 (t, J=8.1, 7.8 Hz, IH); Mass (M+Na)=375; HPLC: 97.34%. Isomer B: ¹ H NMR: 3.45-3.6 (m, 3H), 3.6-3.75 (m, 2H), 3.7 (s, 3H), 4.12 (t, J=9, 8.7Hz, IH), 4.32-4.46 (dd, J=16.2Hz, 2H), 5.55 (d, J=9Hz, IH), 6.85 (m, 3H), 7.24

(t, J=8.1, 7.8 Hz, IH); Mass (M+Na)=375; HPLC: 96.3%.

Example 31 : 2-(acetoxytαethyl)-6-('5-(4-ethoxybenzyl)-2H-tetra2ol-2-yl) tetrahvdro- 2H-ρyran-3.4,5-triyl triacetate:

Isomer A: Mp: 131.2-133.7 ⁰ C; ¹ H NMR: 1.39 (t, J=6.9Hz, 3H), 1.76 (s, 3H), 2.03 (s, 3H), 2.07 (s, 3H), 2.08 (s, 3H), 3.99 (q, J=7.2, 6.9 Hz, 2H), 4.18 (m, IH), 4.2 (s, 2H), 4.28 (m, IH), 5.3 (t, J=9.9Hz, IH), 5.4 (t, J= 9.3Hz, IH), 5.88 (t, J=9.6, 9.3 Hz, IH), 6.04 (d, J=9.3 Hz, IH), 6.84 (d, J=8.7 Hz, 2H), 7.2 (d, J=8.7 Hz, 2H); HPLC: 98.76%; Mass (M+Na)=557.

Isomer B: Mp: 131.7-147.8 ⁰ C; ¹ H NMR: 1.42 (t, J=6.9 Hz, 3H), 1.83 (s, 3H), 2.0- 2.08 (3 s, 9H), 3.71 (m, IH), 4.02 (q, J=7.2, 6.Hz, 2H), 4.22 (m, IH), 4.32 (s, 2H), 5.21 (m, IH), 5.3 (m, IH), 5.55 (m, 2H), 6.88 (d, J=8.7 Hz, 2H), 7.17 (d, J=8.7 Hz, 2H); HPLC: 99.3%; Mass (M+Na)=557.

Example 32: 2-(5-(4-ethoxybenzylV2H-tetrazol-2-ylV6-fhydroxymethγl)tetr ahvdro-

2H-ρvran-3.4,5-triol:

Isomer A: Mp: 79.5-86.4 ⁰ C; ¹ H NMR: 1.36 (t, J= 7.2, 6.9 Hz, 3H), 3.42-355 (m, 3H), 3.67 (m, IH), 4.0 (q, J=I 2, 6.9 Hz, 2H), 4.1 (m, 3H), 4.35 (d, 2H), 5.5 (d, J=9.3

Hz, IH), 6.88 (d, J=8.7 Hz, 2H), 7.2 (d, J=8.7 Hz, 2H); HPLC: 98.68%; Mass (M+Na)=389.

Isomer B: Mp: 79.5-86.4 ⁰ C; ¹ H NMR: 1.35 (t, J=7.2, 6.9 Hz, 3H) ₅ 3.48 (t ₅ J=7.2, 6.9 Hz, IH), 3.52-3.72 (m, 2H), 3.88 (m, 2H), 4.0 (q, J=7.2, 6.9 Hz, 2H), 4.12 (d, IH), 4.18 (s, 2H), 5.84 (d, J=9 Hz, IH), 6.83 (d, J=8.7 Hz, 2H), 7.20 (d, J=8.7 Hz, 2H); HPLC: 96.90%; Mass (M+Na)=389.

Example 33 : 2-facetoxymethyl)-4-hvdroxy-6-f5-f4-isopropoxybenzyl)-2H-tet razol- 2-vDtetrahydro-2H-pyran-3 ,5-diyl diacetate:

^! H NMR: 1.31 (2s, 6H), 1.83(s, 3H), 1.75 (s, 3H), 2.03-2.08 (3s, 9H), 4.0 (m, IH), 4.15 (m, IH), 4.2 (s, 2H), 4.28 (dd, J=12.6 Hz, IH), 4.5 (m,lH), 5.29 (t, J=9.9 Hz, IH), 5.38 (t, J=9.3 Hz, IH), 5.89 (t, J=8.7 Hz, IH), 6.03 (d, J=9.3 Hz, IH), 6.83 (d, J=8.7 Hz, 2H), 7.20 (d, J=8.7 Hz, 2H); Mass (M+Na)=571.

Example 34: 2-(hvdroxymethyl)-6-f5-f4-isopropoxybenzyl)-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3A5-triol:

Yield: 76 %; ¹ H NMR: 1.23 (2s, 6H), 3.2 (m, IH), 3.2-3.55 (m, 3H), 3.68 (m, IH), 3.85 (m, IH), 4.53 (m, IH), 4.6 (t, /=5.7 Hz, IH), 5.22 (d, J=5.4 Hz, IH), 5.3 (d, J=5.4 Hz, IH), 5.51 (d, J=6 Hz, IH), 5.81(d, J=9.3 Hz, IH), 6.85 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H); HPLC: 98.3%; Mass (M+Na)=403.

Example 35: ethyl f3.4,5-trihydroxy-6-(5-(4-isopropoxybenzyl)-2H-tetrazol-2- yl)tetrahvdro-2H-pyran-2-yl)methyl carbonate:

Yield: 71 %; ¹ H NMR: 1.16 (t, J=7.2, 3H), 1.23 (2s, 6H), 3.35 (m, 2H), 3.85 (m, 2H), 4.1 (m, 3H), 4.17 (s, 2H), 4.56 ( m,lH), 4.55 (m, IH), 5.52 (d, J=5.4 Hz, IH), 5.59 (d, J=6 Hz, IH), 5.92 (d, J=9.3 Hz, IH), 6.85 (d, J=8.7 Hz, 2H), 8.4 (d, J=8.7 Hz, 2H); HPLC: 95.8%; Mass (M+Na)=475.

Example 36: 2-(acetoxymethyl ^' )-6-(5-f4-benzylbenzyl)-2H-tetrazol-2-yl)tetrahvdro- 2H-t)yran-3 A5-triyl triacetate:

Isomer A: Mp: 128.8-129.9 ⁰ C; IR :1746, 1224 cm ^'1 ; ¹ H NMR: 1.7 (s, 3H), 2.0-2.1 (s, 9H), 3.95 (s, 2H), 4.0 (m, IH), 4.15 (d, IH), 4.2 (s , 2H), 4.3 (dd, IH), 5.3 (t, IH), 5.35 (t, IH), 5.85 (t, IH), 6.05 (s, IH), 7.1-7.3 (m, 9H); HPLC: 99.92%; Mass (M+Na)=603.

Isomer B: Mp: 184-185 ⁰ C; IR: 1752, 1742, 1225 cm ^'1 ; ¹ H NMR: 1.8 (s, 3H), 2.05 (s, 9H), 3.65 (m, IH), 3.9 (d, IH), 3.95 (S, 2H), 4.15 (dd, IH), 4.35 (s, 2H), 5.2 (t, IH), 5.25 (t, IH), 5.6 (m, 2H), 7.1-7.3 (m, 9H); Mass (M+l)=581; HPLC: 98.19%.

Example 37: 2-(5-(4-benzylbenzyl)-2H-tetrazol-2-yl)-6-(hydroxymethyl)tet rahydro-

2H-pyran-3A5-triol:

Isomer A: MP: 100.1-101.2 ⁰ C; IR: 3351, 1665, 1361 cm ^"1 ; ¹ H NMR: 3.5 (m, 4H), 3.7 (m, 2H), 3.8 (s, 2H), 4.1 (s, 3H), 4.5 (d, 2H), 4.8 (s, IH), 5.65 (d, IH), 7.0-7.2 (m, 9H); Mass (M+Na)=435; HPLC: 97.83%.

Isomer B: IR: 3355, 1661, 1393 cm ^"1 ; H ¹ NMR: 3.35-3.45 (m, 3H), 3.45-3.75 (m, 2H), 3.95 (s, 2H), 4.1 (t, IH), 4.4 (d, IH), 4.65 (brs, 6H), 5.5 (d, IH), , 7.1-7.3 (m, 9H); Mass (M+Na)=435; HPLC: 92.2%.

Example 38: Preparation of 2-facetoxymethyl)-6-f4-ff2-ethyl-2H-tetrazol-5- yl)methyl)phenoxy)tetralivdro-2H-pyran-3.4.5 -triyl triacetate :

Step 1: Synthesis of5-(4-(benzyloxy)benzyl)-2-ethyl-2H-tetrazole:

To 5-(4-(benzyloxy)benzyl)-2H-tetrazole (about 0.2 g, 1 equivalent) was taken into acetonitrile, K ₂ CO ₃ (about 0.31 g) and ethyl iodide (about 0.24 g, 2 equivalents) were added and allowed for heat to reflux for about 3 hours. Completion of the reaction was monitored by TLC. The reaction mixture was filtered off through celite pad, washed with acetonitrile and combined organic layers were evaporated. The crude was taken into EtOAc and washed with 5% HCl, water and brine, dried over Na ₂ SO ₄ and concentrated. The resulting crude had two compounds which are separated by column chromatography using 15% EtOAc/Hexane to afford two isomers of title compound.

Isomer-Λ: Yield: 36%; ¹ H NMR (300 MHz, CDCl ₃ ): δ, 1.6 (t, /=7.2 Hz, 3H), 4.15 (s, 2H), 4.6(q, J=7.5Hz,2H),5.05(s,2H,OCH ₂ ) 7.25(d, J=8.7 Hz, 2H, Ar-H), 7.3- 7.45 (m, 5H); Mass [M+l] ⁺ : 294+1=295 (100%).

Isomer-B: Yield: 40%; ¹ H NMR (300 MHz, CDCl ₃ ): δ, 1.35 (t, J=7.2 Hz, 3H), 4.2 (q, J=7.2 Hz, 2H), 4.25 (s, 2H), 5.05 (s, 2H, OCH ₂ ), 6.9 (d, 2H), 7.1 (d, J=8.4Hz, 2H), 7.3-7.45 (m, 5H); Mass [M+l] ⁺ : 294+1=295 (100%).

Step 2: Synthesis of4-((2-ethyl-2H-tetrazol-5-yl)methyl)phenol:

5-(4-(benzyloxy)benzyl)-2-ethyl-2H-tetrazole (step 1, about 2 g) in ethanol, 10% Pd/C ( about Ig) was added at room temperature and stirred for overnight under H ₂ pressure and completion of the reaction monitored by TLC. The reaction mixture was filtered through celite pad and washed with ethanol. The organic layer was allowed for concentration to afford the title compound.

Isomer A: Yield: 66%; ¹ H NMR (300 MHz, CDCl ₃ ): δ, 1.6 (t, J=I 2, 7.5 Hz, 3H), 4.15 (s, 2H), 4.6 (q, J=I.2 Hz, 2H), 6.45 (brs, IH, OH), 6.7 (d, J=8.7 Hz, 2H), 7.15 (d, J=8.1 Hz, 2H); Mass [M+l] ⁺ : 204+1=205 (100%).

Isomer B: Yield: 72%; ¹ H NMR (300 MHz, CDCl ₃ ): δ, 1.35 (t, J=7.2 Hz, 3H), 4.2 (s, 2H), 4.3 (q, J=7.2Hz, 2H), 6.3 (brs, IH), 6.8 (d, J=8.4 Hz, 2H), 7.05 (d, J=8.7 Hz, 2H); Mass [M+l] ⁺ : 204+1=205 (100%).

Step 3: Preparation of 2-(acetoxymethyl)-6-(4-((2-ethyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3 ,4,5-triyl triacetate:

To 4-((2-ethyl-2H-tetrazol-5-yl)methyl)phenol (step 2, about 1 g, 1 equivalent) in acetonitrile, terra acetyl glucopyranosyl bromide (about 2.6 g, 1.3 equivalent) and anhydride K ₂ CO ₃ (about 2.02 g, 3 equivalents) were added. Contents were stirred at reflux temperature for about 16 hours. Completion of the reaction was monitored by TLC. The reaction mixture was filtered, washed with acetonitrile and filtrate was poured into ice water while stirring then pH was adjusted to 6-7. Extracted with ethyl acetate and washed with 12% brine solution, dried and evaporated. The residue was purified by DIP then again purified by column chromatography to afford the title compound.

Isomer A: Yield: 62 %; ¹ H NMR (300 MHz, CDCl ₃ ): δ 1.6 (t, J=7.2 Hz, 3H), 1.95- 2.2 (4s, 12H), 4.05-4.2 (m, 2H), 4.25-4.35 (m, 2H), 4.6 (q, J=7.2 Hz, 2H), 5.1-5.2 (m, 2H), 5.2-5.4 (m, IH), 5.5 (t, IH), 5.72 (d, IH), 6.75 (d, J=8.7 Hz, 2H), 7.2 (d, J=8.7Hz, 2H); Mass [M+Naf: 534+23 (100%); IR: 1748, 1226 cm ^"1 ; HPLC: 86%. Isomer B: Yield: 68%; ¹ H NMR (300 MHz, CDCl ₃ ): δ 1.35 (t, J=7.5 Hz, 3H), 1.95-

2.15 (4s, 12H), 4.1-4.3 (m, 2H), 4.9 (m, IH), 4.6 (q, J=7.5 Hz, 2H), 5.1 (t, IH), 5.25 (t, IH), 5.45 (d, IH), 5.55 (t, Hz, IH), 6.8 (d, J=8.7 Hz, 2H), 7.0 (d, J=8.7 Hz, 2H); Mass [M+Naf: 534+23 (100%); IR: 1751, 1230, 1039 cm ^"1 ; HPLC: 85%.

Example 39: Preparation of 2-(4-((2-ethyl-2H-tetrazol-5-yl')methyl')phenoxy)-6- divdroxymethvDtetrahvdro-2H-pyran-3,4,5-triol:

2-(acetoxymethyl)-6-(4-((2-ethyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Example 39, about 1 g, 1 equivalent) was added in portion wise to Chilled NH ₃ /CH ₃ OH solution (about 20 ml), and stirred for about 3-4 hours. The reaction mixture was concentrated. The gummy mass obtained was repeatedly washed with hexane and DIP then triturated with MTBE to afford the title compound.

Isomer A: Yield: 63 %; IR: 3325, 1667, 1264 can ^"1 ; ¹ H NMR: 1.56 (t, J=7.2 Hz, 3H), 3.4 (m, 4H), 3.7 (m, IH), 3.89 (m, IH), 4.15 (s, 2H), 4.65 (q, J=7.2 Hz, 2H), 4.9 (s, IH, OH), 7.07 (d, J=8.1 Hz, 2H), 7.25 (d, J=8.1 Hz, 2H); Mass (M+Na)=521; HPLC: 98.2%.

Isomer B: Yield: 67 %; Mp: 181.4-192.1 ⁰ C; IR: 3350, 1513, 1267, 1240 cm ^'1 ; ¹ H NMR: 1.32 (t, J=7.2 Hz, 3H), 3.75 (m, IH), 4.35 (s, 2H), 4.4 (q, J=7.5 Hz, 2H), 4.65 (t, J=5.7Hz, IH), 4.9 (d, J=7.5Hz, IH, OH), 5.15 (d, J=5.1Hz, IH, OH), 5.22 (d, J=4.5Hz, IH), 5.22 (d, J=4.8 Hz, IH, OH), 7.07 (d, J=8.7Hz, 2H), 7.25 (d, J=8.4Hz, 2H); Mass (M+Na)=389; HPLC: 94.81%.

Similarly, the following compounds have been prepared by above procedure with corresponding starting materials:

Example 40: 2-(acetoxymethyl)-6-f4-(Y2-methyl-2H-tetrazol-5- yl)methyl)phenoxy)tetrahvdro-2H-pyran-3 ,4,5-triyl triacetate:

Isomer A: Yield: 75 %; Mp: 99.5-103.1 ⁰ C; IR: 1751, 1742, 1225 cm ^"1 ; ¹ H NMR: 2.02-2.15 (4s, 12H), 3.88 (m, IH), 4.25 (m, 3H), 4.3 (dd, IH), 4.35 (s, 3H), 5.06 (d, IH), 5.2 (t, IH), 5.3 (m, 2H), 6.95 (d, /=8.4 Hz, 2H), 7.3 (d, J=8.4 Hz, 2H); Mass (M+l)=521 (100 %); HPLC: 98.2%. Isomer B: Yield: 71 %; Mp: 173.0-176.0 ⁰ C; IR: 1754, 1742, 1231, 1210 cm ⁴ ; ¹ H NMR: 2.02-2.1 (4s, 12H), 2.19 (s, 2H) ₅ 3.88 (s, 3H) ₃ 4.18 (m, IH), 4.25 (m, 3H), 5.08 (d, J=7.5 Hz, IH), 5.18 (t, J=9.9 Hz, IH), 5.25-5.32 (m, 2H), 6.97(d, J=8.7 Hz, 2H), 7.15 (d, J=8.7 Hz, 2H); Mass (M+Na)=543 (100 %); HPLC: 90.6%.

Example 41j 2-fhydroxmethyl)-6-f4-(f2-methyl-2H-tetrazol-5- yl)memyl)phenoxy)tetrahvdro-2H-pyran-3A5-triol:

Isomer A: Yield: 65 %; IR: 3356, 1663, 1394, 1234 cm ^"1 ; ¹ H NMR: 3.65 (m, IH), 4.15 (s, 2H), 4.3 (s, 3H), 4.58 (t, J=5.7 Hz, IH), 4.8 (d, J=7.2 Hz, IH), 5.05 (d,

J=5.1 Hz, IH), 5.12 (d, J=4.5 Hz, IH), 5.32(d, J=4.8 Hz, IH), 6.7 (brs, 2H,), 6.95

(d, J=8.4 Hz, 2H), 7.2 (d, J=8.7 Hz ₃ 2H) ₃ 7.3 (brs ₃ 2H, ); Mass (M+Na)=375(100 %);

HPLC: 75 %.

Isomer B: Yield: 65 %; IR: 3365, 1661, 1396, 1235 cm ^"1 ; ¹ H NMR: 3.2 (d, IH), 3.68 (dd, IH), 3.95 (s, 3H), 4.25 (s, 2H), 4.6 (t, J=5.7 Hz, IH), 4.82 (d, J=7.2 Hz ₃

IH), 5.05 (d, J=5.4 Hz, IH), 5.12 (d, J=4.2 Hz, IH), 5.32 (d, J=4.8 Hz, IH), 6.7

(brs, 2H), 7.0 (d, J=8.7 Hz, 2H), 7.2 (d, J=8.4 Hz, 2H), 7.3 (brs, 2H); Mass

(M+Na)=375 (100 %); HPLC: 92.5%.

Example 42: Preparation of 2-(acetoxymethγl)-6-(5-(2-oxo-2-(l- phenylethylamino)ethyl)-2H-tetrazol-2-yl)tetrahvdro-2H-pyran -3.4.5-triyl triacetate:

Step 1: synthesis of2-cyano-N-(l-phenylethyl)acetamide: Phenyl ethyl amine (about 4.2 g, 1 equivalent), cyano acetic acid (about 3 g,

1 equivalent), 1 -(3 -dimethyl aminopropyl)-3 -ethyl carbodiimide hydrochloride (about 1.5 equivalent) and 1-hydroxy-benzotriazole (about 4.72 g, 1 equivalent) were added to DMF (50 ml) and stirred at room temperature for about 24 hours. Completion of the reaction was monitored by TLC. The reaction mixture was poured into ice-cold water and acidified with 10% HCl [p ^H 3-4] then extracted with ethyl acetate (3x25 ml). The combined organic layers were washed with water, brine, dried over Na ₂ So ₄ and concentrated under reduced pressure. The residue was purified by precipitation with dichloromethane/n-hexane to afford the title compound Yield: 70 %; ¹ HNMR (300 MHz, CDCl ₃ ): δ 1.55 (d, J=6.9Hz, 3H, CH ₃ ), 3.36 (s, 2H), 5.1 (m, IH), 6.3 (brs, IH), 7.26-7.37 (m, 5H); Mass [M+Naf: 211 (100%).

Step-2: synthesis ofN-(l-phenylethyl)-2-(2H-tetrazol-5-yl)acetamide:

A mixture of 2~cyano-N-(l-phenylethyl)acetamide (step 1, 2.5 g, 1 equivalent), sodiumazide (about 3.8 g, 4.7 equivalents) and zinc bromide (about 4.2 g, 0.7 equivalents), was taken in IPA/H ₂ O (15 ml/45 ml) was refluxed at about 80°C under stirring for about 72 hours. Completion of the reaction was monitored by TLC. The reaction mixture was cooled to room temperature and the P ^H was adjusted to 1.0 with diluted HCl and stirred for about 10 minutes then extracted with ethyl acetate (3x50 ml). The combined organic layers were washed with NaHCO ₃ solution, brine solution, dried over magnesium sulphate (MgSO ₄ ) and concentrated in vacuo to afford the title compound as a white solid. ¹ H NMR (300 MHz, CDCl ₃ ): δ 1.55 (d, J=6.9Hz, 3H CH ₃ ), 3.38 (s, 2H), 5.01 (m, IH), 7.18-7.28 (m, 5H), 7.8 (brs, IH); Mass [M+Na] ⁺ : 254 (100%).

Step 3: Preparation of 2-(acetoxymethyl)-6-(5-(2-oxo-2-(l- phenylethylamino)ethyl)-2H-tetrazol-2-yl)tetrahydro-2H-pyran -3,4,5-triyl triacetate:

To a mixture of N-(l-phenylethyl)-2-(2H-tetrazol-5-yl)acetamide (step 2, about 1.5 g, 1 equivalent), terra acetyl bromoglucose (about 3.46 g, 1.3 equivalent), anhydrous K ₂ CO ₃ (about 2.6 g, 3 equivalent) in acetonitrile (30 ml) was refluxed at about 80°C for about 3 hours and completion of the reaction monitored by TLC. The reaction mixture was filtered, washed with CH ₃ CN and filtrate was poured into ice water while stirring then extracted with ethyl acetate (3x10 ml) and washed with water and brine solution. Solvent was removed under reduced pressure to give crude compound and which was purified by silica gel column chromatography using 20 % EtOAc: Hexane to afford the title compound. Yield: 62 %; Mp: 128-135.5 ⁰ C; IR: 3386, 1750, 1223 cm ¹ ; ¹ H NMR: (1.5d, 3H), 1.7(s, 3H), 2.05 (s, 3H), 2.1 (s, 6H), 4.0 (s, 2H), 4.05 (dd, Ih), 4.2 (d, IH), 4.35 (dd, IH), 5.2 (m, IH), 5.3 (t, IH), 5.45

(t, IH), 5.65 (t, IH), 6.05 (d, IH), 6.6 (d, IH), 7.3 (m, 6H, Ar-H); HPLC:98.27%; Mass (M+Na)=584.

Example 43: Preparation of N-Q-phenylethylV2-f2-f3A5-trihvdroxy-6- fhydroxymethyl)tetrahydro-2H-pyran-2-yl ^' )-2H-tetrazol-5-yl')acetamide:

2-(acetoxymethyl)-6-(5-(2-oxo-2-(l-phenylethylamino)ethyl )-2H-tetrazol-2- yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Example 42, about 1 g) was added in portions wise to the cold NH ₃ /CH ₃ OH solution (about 30 ml), and stirred for about 3 hours at room temperature then the reaction mixture was allowed for concentration under reduced pressure. The residue was taken in to ethyl acetate and washed with saturated brine solution (2x50 ml), dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to afford the title compound. Yield: 50 %; MP: 102-122 ⁰ C; IR: 3347, 1659, 1097 cm ^"1 ; ¹ H NMR: 1.4 (d, CH3), 3.2 (m, 2H), 3.5 (m, 2h), 3.7 (m, Ih), 3.9 (m, 3H), 4.75 (m, IH), 5.2 (d, IH), 5.3 (d, IH), 5.5 (d, IH), 5.85 (d, IH), 6.7 (brs, IH),

7.3 (m, 5H, Ar-H); HPLC: 99.63%; Mass (M+Na)= 416.

Similarly, the following compounds have been prepared by above procedure with corresponding starting materials:

Example 44: 2-facetoxymethyiy6-f 5-(2-f 1 -( ^" 4-methoxyρhenyl)ethylaminoV2- oxoethyl)-2H-tetrazol-2-yl)tetrahvdro-2H-pyran-3.4.5-triyl triacetate:

MP:159-161.3.°C; IR:3398,1750,1658,1217 cm ^'1 ; ¹ H NMR: 1.35(d,3H), 1.8(s,3H), 1.9-2.1(3 s,9H), 3.75(s,3H), 3.85(s,2H), 4.05(d,lH), 4.2(dd,lH), 4.45(m,lH), 4.85(t,3H), 5.15(t,3H), 5.6(m,2H), 6.7(d,lH), 6.9(d,2H), 7.2(d,2H), 8.65(d,lH); Mass (M+Na)=614; HPLC:96.51%.

Example 45j N-(I -f4-methoxyphenvnethylV2-f2-(3.4.5-trihvdroxy-6-

(hydroxymethyl ^' )tetrahvdro-2H-pyran-2-yl)-2H-tetrazol-5-yl)acetamide:

MP 91.5-116.8 ⁰ C; IR:3354,1661, 1645,1251 cm ^"1 ; ¹ H NMR: 1.35(d,3H), 3.2(m,lH), 3.5(m,2H), 3.7(m,4H), 3.85(m&s,3H), 4.75(m,lH), 4.85(m,lH), 5.25(d,lH),

5.35(d,lH), 5.5(d,lH), 2.85(d,lH), 6.7(brs,lH), 6.9(d,2H), 7.3(d,2H), 8.7(d,lH); Mass: 423+23=446 (molecular ion peak); HPLC:96.53%

Pharmacological activity The compounds described herein can be tested for their activity for SGLT2 inhibitors following any procedures known to a person of ordinary skill in the art. For example, the following protocols may be employed for testing the compounds. These protocols are illustrative and do not limit to the scope of the invention. Example 46: Screening the activity of SGLT inhibitor in the rat renal BBMVs (Brush border membrane vesicles):

Brush border membrane vesicles were prepared from renal tissues of normal rats by the MgCl ₂ precipitation method (Jurg Biber et al., 2007). Na+-glucose co transporter activity (SGLT) was detennined by the rapid filtration method (Biochem. Biophys. Acta, 554: 259-273, 1979). Glucose uptake was initiated by mixing 10 μL (100 μg) of the BBMV membrane with 50 μL of buffer (100 mmol mannitol, 100 mmol NaCl and 10 mmol HEPES-Tris) containing D-[6 — ³ H(N)] glucose (1 μCi, NEN, Boston, MA, USA) and test compounds. Then the reaction was terminated after ten seconds by diluting the 60 μL reaction mixture with 1 mL of ice-cold stop solution (300 mmol mannitol, 80 mmol Na2SO4, 10 mmol Tris H2SO4 and 0.3 mmol phlorizin pH 7.4), which was then filtered through wet Millipore filters (0.45 μm pore size) and kept under suction. The filters were washed twice with 1 mL of ice-cold stop solution and dissolved in 5 niL of scintillation fluid, and the experiments were performed in triplicate. The radioactivity on the membrane was measured with a liquid scintillation counter (Tricarb).

The above described examples were tested in this biological assay described above and were found following results as shown in table 1 at two different concentrations like 10 μm and 3 μm.

Table- 1

Example 47: Screening the activity of SGLT inhibitor in the rat cell based assay:

Cloning of rSGLT-2 and transferring to expression vector:

The total RNA of SD-Rat Kidney was reverse transcribed in to cDNA for PCR amplification using oligo-dT primers. By means of cDNA as a template, base sequence encoding Rat SGLT-2 (Accession number NM_022590, sequence from 6 to 2018) was amplified by PCR and inserted in to the multiple cloning site of pCl- neo vector (Promega). The base sequence of inserted DNA completely matched with the reported sequence.

Preparation of cells transiently expressing Rat SGLT2:

The above described plasmid pCl-neo carrying Rat SGLT2 DNA sequence was transfected to COS-7 cells by Lipofection method. Lipofectamine-2000 reagent (Invitrogen) was used as the lipofection reagent. The day before transfection plate 1.2 X 10 ⁵ cells in 500 μl of growth medium Dulbecco's modified Eagle's medium, high glucose, pyridoxine HCl, and 25 mM HEPES (Invitrogen) supplemented with 10% heat-inactivated fetal bovine serum (Invitrogen), 100 units/ml penicillin, and lOOμg/ml streptomycin at 37 ⁰ C in 5% CO2. Cells were plated on 24-well flat bottom plates (BD biosciences). For each well 0.2 μg of Rat SGLT-2 plasmid was diluted in 50μl of plain DMEM and 0.6 μl of Lipofectamoine-2000 reagent in 50 μl of plain DMEM and combine both DNA and Lipofectamine mix after 5 min and keep for incubation for 20 min then add in to the well and replace the medium after 5hrs. Inhibition assay of Methyl-ά-D-glucopyranoside uptake activity:

Transport assays were carried out 48 h after transfections as described previously except that all steps were done at 37°C (Pajor and Valmonte, 1996). The sodium buffer contained 14OmM NaCl, 2 mM KCl, 1 mM MgC12, 1 mM CaC12, and 10 mM HEPES, pH adjusted to 7.4 with 1 M Tris. Choline buffer contained 140 mM choline chloride in place of NaCl. For the assays, each well was washed twice with 1 ml of choline buffer, then incubated with 0.2 ml of sodium buffer containing [14C]α-methyl-D-glucopyranoside for 60 min . Inhibitors were added to the transport solutions from dimethyl sulfoxide stocks, with a final volume of dimethyl sulfoxide less than 0.5%. The plates were incubated at 37 ⁰ C. The uptakes were stopped and extra cellular radioactivity removed with two 1-ml washes of choline buffer. After the last wash was removed, each well of cells was solubilized in 200 mM NaOH then transferred in to picoplates (Perkin Elmer) mixed with 1 ml of scintillation cocktail (Microscint-40, Perkin Elmer). The plates were sealed with plastic plate covers total counts per minute measured on the gamma counter (Top

Count Perkin Elmer). The uptake obtained by untreated cells (control wells) was considered as a 100% uptake. The reductions in CPMA in the drug treated wells with respect to control was expressed as % inhibition and calculated by the following formula:

% Inhibition= CPMA (control)-CPMA (treated) X 100

CPMA (control)

The above described examples were tested in this biological assay described above and were found following results as shown in table 2 at 3 μm concentration. Table-2

Example 48: Assay for the effect on urinary glucose excretion:

As experimental animals, overnight fasted SD rats male, 7-8 weeks age, 230- 250grams were used. The test compound was suspended with a solution of 5 % 1- methyl 2- pyrrolidinone, 20% polyethylene glycol (400), 20 mmol/ 1 sodium diphosphate (Tetra basic) and the suspension was used for administration. On the day before drug administration, the rats were transferred in metabolic cages and tested from the evening. Throughout the study, the rats were given water and libitum. The test compound was orally administered at the dose of lOmg/ kg and urine collection was performed for 24hrs after the compound administration. The rats were fed ad libitum from 4 hrs after the compound administration. The volume of urine collected was measured and apart of urine was used as a sample for glucose concentration measurement. The samples were diluted as appropriate and the glucose concentrations were measured.

The above described examples were tested in this biological assay described above and were found following results as shown in table 3.

Table-3

References:

1. Am Jphysiol Renal Physiol 286, Fl 27-Fl 33, 2004;

2. Nature protocols, 2007, 2(6), 1356-59;

3. J. Pharmacology and Experimental Therapeutics, 324, 985-991, 2008.

Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as described above.

All publications and patent applications cited in this application are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated herein by reference.