cas 461432-22-4, (5-bromo-2-chlorophenyl)(4-ethoxyphenyl)methanone

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PREPARATION OF HIGHLY PURE AMORPHOUS DAPAGLIFLOZIN
A novel and improved process for the preparation of amorphous dapagliflozin is disclosed. The present invention further provides pharmaceutical compositions containing amorphous dapagliflozin, optionally in a combination with one or more other active substances and methods for making the same.
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Page/Page column 23-24

(2021/12/13)

Copper-Catalyzed Cross-Coupling of Benzylic C-H Bonds and Azoles with ControlledN-Site Selectivity
Azoles are important motifs in medicinal chemistry, and elaboration of their structures via direct N-H/C-H coupling could have broad utility in drug discovery. The ambident reactivity of many azoles, however, presents significant selectivity challenges. Here, we report a copper-catalyzed method that achieves site-selective cross-coupling of pyrazoles and other N-H heterocycles with substrates bearing (hetero)benzylic C-H bonds. ExcellentN-site selectivity is achieved, with the preferred site controlled by the identity of co-catalytic additives. This cross-coupling strategy features broad scope for both the N-H heterocycle and benzylic C-H coupling partners, enabling application of this method to complex molecule synthesis and medicinal chemistry.
Chen, Si-Jie,Golden, Dung L.,Krska, Shane W.,Stahl, Shannon S.
supporting information
p. 14438 - 14444
(2021/09/18)

Preparation method of polysubstituted diphenyl ketone
The preparation method comprises the following steps: (1) a compound represented by the formula II and a compound shown III as a raw material; and synthesizing the compound as shown IV. (2) The compound of Formula IV is subjected to Fries rearrangement to produce a compound of Formula V. (3) A compound of Formula V is subjected to a halogenation reaction in contact with a halogenation reagent to prepare a multi-substituted diphenyl ketone represented by Formula I. Wherein, X is selected from H, F, Cl, Br, I. R1 Selected H from F Cl, Br I are RO selected R from H, C1 - C6. X is selected from F, Cl, Br, and i. The present invention is capable of improving the yield and selectivity of the target product.
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(2021/09/21)

METHOD FOR MANUFACTURING DIARYLMETHANE COMPOUND
An object is to provide a method for producing a compound which is useful as a synthetic intermediate for an active pharmaceutical ingredient of an antidiabetic drug or the like in an industrially inexpensive and efficient manner, and the present invention can achieve the object by reducing a compound (2) represented by the following formula (2): wherein R1, Ar, n and X are as mentioned herein in the presence of a titanium compound by using a reducing agent to produce a compound (1) represented by the following formula (1): wherein R1, Ar and n are the same as defined above.
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Paragraph 0233-0234

(2021/07/02)

Method for preparing dapagliflozin intermediate by one-pot method
The invention discloses a method for preparing a dapagliflozin intermediate by a one-pot method, and the method comprises the following steps: reacting 5-bromo-2-chlorobenzoic acid with phenetole in the presence of an oxidant and a catalyst for a period of time, and performing purifying to obtain the dapagliflozin intermediate (5-bromo-2-chlorphenyl) (4-ethoxyphenyl) ketone. The method provided by the invention is high in yield, simplifies the process steps of the traditional synthesis method, makes the process simpler, reduces the reaction cost and impurity content, improves the purity and yield, and better conforms to the industrialization standard of benefit maximization.
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Paragraph 0033-0052

(2021/06/09)

Combined catalyst for use in specific Friedel-Crafts reactions
The invention provides an application of a ferric trichloride and indium trichloride combined catalyst in a specific Friedel-Crafts reaction, more specifically, the invention provides an application of a ferric trichloride and indium trichloride combined Lewis acid catalyst in preparation of a key intermediate of empagliflozin, dapagliflozin and canagliflozin drugs. Compared with the prior art, the ferric trichloride and indium trichloride combined catalyst provided by the invention can greatly reduce the use of inorganic salt in the preparation process of the key intermediate of the empagliflozin, dapagliflozin and canagliflozin drugs, and obviously reduce the emission of waste water, waste gases and waste residues; and the ferric trichloride and indium trichloride combined catalyst can significantly improve the selectivity of para-position products in the preparation process of the key intermediate of the empagliflozin, dapagliflozin and canagliflozin drugs, can remarkably improve the quality and the yield of a target product, and remarkably reduce the process cost.
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Paragraph 0058; 0060-0064; 0066-0069; 0071-0074

(2020/12/10)

Preparation method of 5-bromo-2-chloro-4'-ethoxybenzophenone
The invention discloses a preparation method of 5-bromo-2-chloro-4'-ethoxybenzophenone, and belongs to the technical field of medicine synthesis. The preparation method comprises the following steps:(1) carrying out direct reflux reaction on 5-bromo-2-chlorobenzoic acid and thionyl chloride in the absence of a solvent under the catalysis of DMF, and evaporating excessive thionyl chloride to obtain 5-bromo-2-chlorobenzoyl chloride after the reaction is finished; (2) adding dichloromethane into the material obtained in the step (1) for dissolving, directly adding silica gel loaded aluminum trichloride, performing reacting with phenethyl ether under a vacuum condition, performing filtering after the reaction is completed, washing the filtrate with a 5% sodium bicarbonate solution and water in sequence, performing evaporating to remove the solvent, and performing recrystallizing with a mixed solvent of ethanol and water to obtain 5-bromo-2-chloro-4'-ethoxybenzophenone. The method providedby the invention has the advantages of the small acid solvent generation amount, less difficult-to-treat wastewater, high product purity and yield, no generation of by-products, environmental protection, simple operation, and suitability for industrial production and popularization.
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Paragraph 0025; 0027-0028; 0030-0031; 0033-0034; 0036-0037

(2020/05/14)

Preparation method of 5-bromo-2-chloro-4 '-ethoxydiphenylmethane
The invention relates to a preparation method of 5-bromo-2-chloro-4 '-ethoxydiphenylmethane. The preparation method is characterized by comprising the following steps: step S1, preparation of 5-bromo-2-chlorobenzoyl chloride, step S2, preparation of 5-bromo-2-chloro-4'-ethoxybenzophenone, and step S3, preparation of 5-bromo-2-chloro-4 '-ethoxydiphenylmethane. The invention further discloses the 5-bromine-2-chloro-4 '-ethoxydiphenylmethane prepared according to the preparation method of the 5-bromine-2-chloro-4'-ethoxydiphenylmethane. The invention further discloses the 5-bromine-2-chloro-4 '-ethoxydiphenylmethane prepared according to the preparation method of the 5-bromine-2-chloro-4'-ethoxydiphenylmethane. According to the preparation method of the 5-bromo-2-chloro-4 '-ethoxydiphenylmethane, traditional preparation process conditions are optimized and innovated, the method effectively improves the product purity, the reaction conversion rate and the production efficiency, has no special requirements on reaction conditions and equipment, is suitable for industrial production, causes less pollution to the environment and effectively realizes good combination of economic benefits, social benefits and ecological benefits.
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Paragraph 0034; 0037; 0044-0060

(2020/09/23)

PROCESS FOR THE PREPARATION OF SOTAGLIFLOZIN
Sotagliflozin may be prepared using schemes and intermediates disclosed herein. Sotagliflozin may be incorporated into pharmaceutical dosage forms for treatment of diabetes.
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Page/Page column 45; 46

(2019/09/18)

Design, synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents
The cardiovascular complications were highly prevalent in type 2 diabetes mellitus (T2DM), even at the early stage of T2DM or the state of intensive glycemic control. Therefore, there is an urgent need for the intervention of cardiovascular complications in T2DM. Herein, the new hybrids of NO donor and SGLT2 inhibitor were design to achieve dual effects of anti-hyperglycemic and anti-thrombosis. As expected, the preferred hybrid 2 exhibited moderate SGLT2 inhibitory effects and anti-platelet aggregation activities, and its anti-platelet effect mediated by NO was also confirmed in the presence of NO scavenger. Moreover, compound 2 revealed significantly hypoglycemic effects and excretion of urinary glucose during an oral glucose tolerance test in mice. Potent and multifunctional hybrid, such as compound 2, is expected as a potential candidate for the intervention of cardiovascular complications in T2DM.
Li, Zheng,Xu, Xue,Deng, Liming,Liao, Ruoxian,Liang, Ruiying,Zhang, Bo,Zhang, Luyong
p. 3947 - 3952
(2018/06/27)

6-halogenated glucose C-glycoside as well as preparation method and application thereof
The invention discloses a 6-halogenated glucose C-glycoside as well as a preparation method and application thereof. A structure of 6-halogenated glucose C-glycoside is shown in formula I; an intermediate can be synthesized efficiently with cheap and easily available raw materials; meanwhile, when the raw material is used for synthesizing Jardiance, dapagliflozin and the like, a reaction yield ishigh, and an obtained product has high purity and relatively high industrial application prospect.
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Paragraph 0072; 0073; 0075; 0076

(2018/11/03)

Studies towards the synthesis of ertugliflozin from L-Arabinose
A new method for the diastereoselective synthesis of enantiomerically pure ertugliflozin was developed. The crucial step involves an aldol condensation between 1-(4-chloro-3-(4-ethoxybenzyl)phenyl)ethanone and (4R,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyl-5-((trityloxy)methyl)-1,3-dioxolane-4-carbaldehyde, which was prepared from known 2-C-trityloxymethyl-2,3-O-isopropylidene-L-erythrose (easily accessible in three steps from L-arabinose) by standard reduction/oxidation and protection/deprotection manipulations. Dihydroxylation of the aldol condensation product and further global deprotection led to the formation of the target molecule.
Triantakonstanti, Virginia V.,Mountanea, Olga G.,Papoulidou, Kyriaki-Eleni C.,Andreou, Thanos,Koftis, Theocharis V.,Gallos, John K.
p. 5700 - 5708
(2018/08/20)

A SGLT2 inhibitor intermediates preparation method (by machine translation)
The invention discloses a SGLT2 inhibitor intermediates preparation method, comprises the following steps: (1) 5 - halo - 2 - chlorobenzoic acid and fluorobenzene to Friedel-crafts reaction, to obtain (5 - halo - 2 - chlorophenyl) (4 - fluorophenyl) a ketone; (2) under the action of the inorganic base, (5 - halo - 2 - chlorophenyl) (4 - fluorophenyl) methanone and ethanol undergo the substitution reaction, after the reaction is finished after treatment to obtain (5 - halo - 2 - chlorophenyl) (4 - ethoxy) a ketone; (3) (5 - halo - 2 - chlorophenyl) (4 - ethoxy) methanone in the reducing agent under the effect of the reduction reaction of carbonyl, get said SGLT2 inhibitor intermediates. The preparation method is through adopting the inorganic alkali and ethanol instead of the ethoxide reagent and DMSO (or DMF), not only can effectively reduce the cost, but also more environmentally friendly. (by machine translation)
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(2018/11/22)

Dicyclic derivative of glucoside as well as preparation method and application of dicyclic derivative
The invention relates to a dicyclic derivative of glucoside as well as a preparation method and the application of the dicyclic derivative. Specifically, the invention relates to a compound as shown in Formula I, a stereisomer or pharmaceutically acceptable salt or ester of the compound, a pharmaceutical composition of the compound, and application of the compound in preparation of drugs for treating diabetes or relevant diseases.
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Paragraph 0176; 0177; 0178

(2018/07/30)

Preparation method of Dapagliflozin intermediate used for treating II-type diabetes
The invention discloses a preparation method of a Dapagliflozin intermediate used for treating II-type diabetes. The preparation method comprises the following steps: 1) performing a reaction on 5-bromine-2-chlorobenzoic acid and oxalyl chloride in anhydrous dichloromethane under the catalysis of DMF (dimethyl formamide), so as to obtain 5-bromine-2-chloro-benzoyl chloride; 2) under the condition that tert-Butyldimethylsilyl chloride exists, performing a reaction on 5-bromine-2-chloro-benzoyl chloride obtained in step 1) and phenetole under the catalysis of ferric trichloride, so as to obtain 5-bromine-2-chloro-4'-ethyoxyl benzophenone. According to the preparation method provided by the invention, no ortho-by-product is generated, and the yield of a target product is high, so that the good support of storage of raw materials is provided for Dapagliflozin. Additionally, the preparation method is mild in conditions and short in reaction time, therefore, the preparation method is suitable for industrial production and promotion.
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Paragraph 0029; 0035; 0039; 0043; 0047

(2017/10/10)

Novel method for synthesizing dapagliflozin intermediate compound
The invention discloses a novel method for synthesizing a dapagliflozin intermediate compound. The method comprises the following steps: (1) by taking dichloromethane as a solvent and pyridine as a catalyst, reacting 5-bromo-2-chlorobenzoic acid and thionyl chloride to obtain 5-bromo-2-chlorobenzoyl chloride; (2) by taking dichloromethane as a solvent and solid acid as a catalyst, reacting phenetole and the 5-bromo-2-chlorobenzoyl chloride to obtain 5-bromo-2-chloro-4-ethoxydiphenylketone; and (3) by taking THF as a solvent, adding the 5-bromo-2-chloro-4-ethoxydiphenylketone concentrated solution obtained in the step (2); by taking acetic acid and aluminum trichloride as catalysts, adding sodium borohydride, and performing a reduction reaction; and after the reaction is completed, adding a saturated saline solution, and performing quenching at 25 DEG C or below to obtain 5-bromo-2-chloro-4-ethoxydiphenylmethane. The novel method disclosed by the invention has the advantages of cheap and available raw materials, simple and easy operation, no discharge of three wastes, high reaction yield and the like.
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Paragraph 0030; 0032; 0034; 0036; 0038; 0040

(2018/04/01)

SGLT-2 inhibitor intermediate synthesis method
The invention discloses a SGLT-2 inhibitor intermediate synthesis method. The method utilizes a NaBH4-TMSCl complex reducing agent to reduce carbonyl into methylene. The synthesis method has the characteristics of less side reactions, good environmental friendliness, low price, use of easily available raw materials and large scale production feasibility.
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Paragraph 0014

(2017/08/27)

ISOLATED INTERMEDIATE OF DAPAGLIFLOZIN, PROCESS FOR THE PREPARATION OF ISOLATED INTERMEDIATE OF DAPAGLIFLOZIN, PROCESS FOR THE PREPARATION OF DAPAGLIFLOZIN
Aspects of the present invention relates to an isolated intermediate of Dapagliflozin (Formula III) and its preparation, process for the preparation of Dapagliflozin, process for the preparation of crystalline propane-1,2,3-triol solvate of dapagliflozin, process for the preparation of L-proline complex of Dapagliflozin, solid premix of dapagliflozin with the polymer selected from the group consisting of eudragit, syloid, MCC Avicel PH 102 (1:1) and MCC Avicel PH 102 (1:2).
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Page/Page column 32; 33

(2017/03/28)

PROCESSES FOR THE PREPARATION OF EMPAGLIFLOZIN
The present invention relates to processes for the preparation of empagliflozin. In particular, the present invention relates to the preparation of empagliflozin and intermediates thereof. The present invention also relates to co-crystal of empagliflozin and amino acid and amorphous form of empagliflozin.
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Paragraph 0170; 0177; 0178

(2017/09/13)

A reach geleg only preparation method
The invention relates to a preparation method for Dapagliflozin. The preparation method comprises the following steps that a compound 2 and phenetole are mixed to obtain a mixture, and then the mixture is dropped into a suspended aluminum trichloride solution, so that the content of generated ortho isomer impurities is smaller than 1 percent; a compound 4 in the preparation method is firstly reacted with butyl lithium to generate a compound 5 in the following formula; then the compound 5 is reacted with a compound 1, so that generation of sulphonate type genetic toxic impurities is avoided; therefore the utilization rate of raw materials is increased to a certain extent, the problem of complicated post-treatment is avoided, and the purity and the yield of products are improved. According to the preparation method, a compound 6 is reduced by using hydroboron and sulfuric acid, so that the reduction reaction and deprotection can be simultaneously carried out, and the pollution is greatly alleviated. The raw materials and the reagents which are adopted in the preparation method are relatively cheap and low in cost; meanwhile, the reaction conditions of the whole preparation process are mild, and the operation is simple and safe; industrial production can be conveniently realized.
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Paragraph 0050

(2017/09/01)

Preparation method of 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane
The invention provides a preparation method of 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane. The preparation method comprises the following steps: (1) using 4-hydroxybenzaldehyde and bromoethane as raw materials, a polar solvent as a reaction solvent and inorganic base as a catalyst to react so as to prepare 4-ethoxy-benzaldehyde; (2) using hydroxylamine hydrochloride and 4-hydroxybenzaldehyde as raw materials and a hydroxyl-containing solvent as a reaction solvent to react so as to obtain oxime, and then reacting under the effect of a dehydrating agent so as to generate 4-ethoxyl benzonitrile; (3) using 4-bromaniline and 4-ethoxyl benzonitrile as raw materials, using lewis acid as a catalyst, and performing a Hoesch reaction to generate 5-bromine-2-amino-4'-ethyoxyl benzophenone; (4) performing a diazo-reaction on 5-bromine-2-amino-4'-ethyoxyl benzophenone, and then reacting with cuprous chloride to synthesize 5-bromine-2-chlorine-4'-ethyoxyl benzophenone; and (5) performing a reduction reaction on 5-bromine-2-chlorine-4'-ethyoxyl benzophenone to obtain 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane. The method is low in cost, low in environment stress and short in synthetic route.
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(2017/11/18)

Preparation method of SGLT2 inhibitor intermediate
The invention provides a preparation method of an SGLT2 inhibitor intermediate II. The preparation method includes that a compound V and an ethoxide reagent are subjected to nucleophilic substitution in a proper solution to obtain a compound II, wherein the compounding formula is shown as below, and X in the compound V structure is selected from Br or I. By the compounding route, the problem of purification difficulty caused by plenty of isomers in compounding routes in documentary reports is solved. Reaction operations are simple and convenient, the reagent is low in cost and easy to get, and the obtained product does not contain the isomers. The route is suitable for industrial production.
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Paragraph 0048-0049

(2017/08/30)

Cu(II)-Catalyzed Ligand-Free Oxidation of Diarylmethanes and Second Alcohols in Water
We developed a simple and efficient Cu(II)-catalyzed ligand-free oxidation of diarylmethanes and secondary alcohols using 70% tert-butyl hydroperoxide (TBHP) in water. A series of diarylmethanes were directly oxidized into diaryl ketones in 67%–98% yields. Additionally, various secondary alcohols were also transformed into the desired products in 48%–98% yields. Importantly, the catalytic system in the absence of any organic solvent, surfactant, or phase transfer agent, had a wide substrate scope and a high tolerance for various functional groups.
Wu, Jianglong,Liu, Yan,Ma, Xiaowei,Liu, Ping,Gu, Chengzhi,Dai, Bin
supporting information
p. 1391 - 139
(2017/09/30)

C- ARYL GLYCOSID DERIVATIVES, PHARMACEUTICAL COMPOSITION, PREPARATION PROCESS AND USES THEREOF
This invention relates to a kind of C-aryl glycoside derivatives, its pharmaceutical compositions, preparation methods, and uses thereof. The preparation method comprises: method 1: in a solvent, deprotecting the acetyl protecting groups of compound 1-f in the presence of a base; method 2: 1) compound 2-g reacts with via Mitsunobu reaction; 2) deprotecting the acetyl protecting groups of compound 2-f obtained from step 1; method 3: 1) compound 2-g reacts with via nucleophilic substitution reaction; 2) deprotecting the acetyl protecting groups of compound 3-f obtained from step 1. The pharmaceutical composition comprises a kind of C-aryl glycoside derivatives; it's pharmaceutically acceptable salts and/or prodrugs thereof and excipient thereof. This invention further relates to a kind of C-aryl glycoside derivatives, it's pharmaceutically acceptable salts or pharmaceutical compositions thereof for the use in preparation of a SGLT inhibitor. The C-aryl glycoside derivatives of this invention provides a new direction for the study of SGLT inhibitors.
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Paragraph 0096; 0336; 0337

(2017/04/19)

PROCESS FOR THE PREPARATION OF (1S)-1,5-ANHYDRO-1-C-{4-CHLORO-3-4[(4-ETHOXYPHENYL)METHYL]PHENYL]-GLUCITOL AND ITS SOLVATE THEREOF
The present invention relates to a process for the preparation of (1S)-1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol which is represented by the following structural formula-1 and its glycerol solvate.
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Paragraph 0075-0076

(2017/02/24)

PROCESSES FOR THE PREPARATION OF ERTUGLIFLOZIN
The present invention relates to processes for the preparation of ertugliflozni. The present invention also provides compounds of Formula (III), Formula (IV), and Formula (VII), processes for their preparation, and their use for the preparation of ertugliflozin. The processes of the present invention involve protecting the ertugliflozin intermediate compound with a suitable protecting group which provides ertugliflozin having high purity and yield.
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Paragraph 0129

(2018/01/04)

C - aryl glucoside SGLT2 inhibitor
The invention relates to the field of medicines related to diabetes mellitus and particularly relates to a 2-type sodium-glucose co-transporter (SGLT2) inhibitor with a multi-aryl glucoside structure and shown as the specification, a preparation method thereof, a medicine composition taking the compound as an active components and an application thereof in preparing medicines for resisting diabetes mellitus.
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Paragraph 0228; 0229

(2017/04/28)

PROCESS FOR PREPARATION OF DAPAGLIFLOZIN
The present invention relates to a process for the preparation of amorphous dapagliflozin. The present invention relates to 2,3-butanediol solvate of dapagliflozin and process for its preparation.
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Paragraph 0189

(2016/11/21)

Inhibitor of Sodium-Dependent Glucose Transport Protein and Preparation Method Therefor and Use Thereof
Disclosed is a compound of formula I, or a pharmaceutically acceptable salt, solvate, polymorph, enantiomer or racemic mixture thereof, wherein R1 and R2 are each independently hydrogen, —OH, alkyl, —CF3, —OCHF2, —OCF3 or halogen; R3 is cycloalkyl, —OCH2CF3, —OCH2CHF2, —OCH2CH2F or —OCH2CH3; R4 is hydrogen, —OH, —O aryl, —OCH2 aryl, alkyl, cycloalkyl, —CF3, —OCHF2, —OCF3, —OCH2CF3, —OCH2CHF2, —OCH2CH2F or halogen; A is —CX1X2, wherein X1 and X2 are each independently H, F and Cl, and when both X1 and X2 are H, R3 is not —OCH2CH3. The compound has an activity of inhibitors of sodium-dependent glucose transport protein. Also disclosed is a method for preparing the compound, a pharmaceutical composition comprising the compound, use of the compound and pharmaceutical composition thereof in preparing medicaments of SGLT2 inhibitors and treating related diseases.
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Paragraph 0074; 0075

(2014/03/24)

PHENYL C-GLUCOSIDE DERIVATIVES, PREPARATION METHODS AND USES THEREOF
The present invention relates to a sodium glucose cotransporter 2 (SGLT2) inhibitor with a phenyl C-glucoside structure, its preparation method, a pharmaceutical composition containing the same, and its use in treating diabetes and preparing an anti-diabetes medicament. The invention provides a compound with the structure of general formula I and a pharmaceutically acceptable salt and prodrug ester thereof, wherein, the definitions of R5 and R6 are selected from the following: (1) R5=R6=Me; (2) R5=Me, R6=OMe; (3) R5=Me, R6=H; (4) R5=Me, R6=F; (5) R5=F, R6=H; and (6) R5=OMe, R6=H.
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Paragraph 0088

(2013/03/26)

Synthesis and biological evaluation of novel C-aryl D-glucofuranosides as sodium-dependent glucose co-transporter 2 inhibitors
Novel C-aryl-d-glucofuranosides were synthesized and evaluated for their capacity to inhibit human sodium-dependent glucose co-transporter 2 (hSGLT2) and hSGLT1. Compound 21q demonstrated the best in vitro inhibitory activity against SGLT2 in this series (EC50 = 0.62 μM).
Lin, Tzung-Sheng,Liw, Ya-Wen,Song, Jen-Shin,Hsieh, Tsung-Chih,Yeh, Hsien-Wei,Hsu, Lih-Ching,Lin, Chun-Jung,Wu, Szu-Huei,Liang, Pi-Hui
p. 6282 - 6291
(2013/10/22)

CYCLOALKYL METHOXYBENZYL PHENYL PYRAN DERIVATIVES AS SODIUM DEPENDENT GLUCOSE CO TRANSPORTER (SGLT2) INHIBITORS
The invention relates to the cycloalkyl methoxybenzyl phenyl pyran derivatives as Sodium dependent glucose co transporter (SGLT) inhibitors, particularly SGLT2 and method of treating diseases, conditions and/or disorders inhibited by SGLT2 with them, and processes for preparing them.
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Page/Page column 20

(2012/03/26)

PHENYL C-GLUCOSIDE DERIVATIVES, PREPARATION METHODS AND USES THEREOF
The present invention relates to a sodium glucose cotransporter 2 (SGLT2) inhibitor with a phenyl C-glucoside structure, its preparation method, a pharmaceutical composition containing the same, and its use in treating diabetes and preparing an anti-diabetes medicament. The invention provides a compound with the structure of general formula I and a pharmaceutically acceptable salt and prodrug ester thereof, wherein, the definitions of R5 and R6 are selected from the following: (1) R5 = R6 = Me; (2) R5 =Me, R6 = OMe; (3) R5 =Me, R6 = H; (4) R5 =Me, R6 = F; (5) R5 = F, R6 = H; and (6) R5 = OMe, R6 = H.
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Page/Page column 14-15

(2012/12/14)

FAMILY OF ARYL, HETEROARYL, O-ARYL AND O-HETEROARYL CARBASUGARS
The present invention relates to a compound of the following formula (I): as well as its process of preparation, pharmaceutical and cosmetics composition comprising it and use thereof, notably as an inhibitor of the sodium-dependent glucose co-transporter, such as SGLTl, SGLT2 and SGLT3, in particular in the treatment or prevention of diabetes, and more particularly type-II diabetes, diabetes-related complications, such as arthritis of the lower extremities, cardiac infarction, renal insufficiency, neuropathy or blindness, hyperglycemia, hyperinsulinemia, obesity, hypertriglyceridemia, X syndrome and arteriosclerosis, as well as for its use as an anticancer, anti-infective, anti-viral, anti-thrombotic or anti- inflammatory drug, or for lightening, bleaching, depigmenting the skin, removing blemishes from the skin, particularly age spots and freckles, or preventing pigmentation of the skin.
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Page/Page column 53

(2012/12/13)

PROCESSES FOR THE PREPARATION OF SGLT2 INHIBITORS
Provided are processes for the preparation of complexes that are useful in purifying compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The processes can reduce the number of steps needed to obtain the target compounds and the complexes formed in the processes are typically provided in a crystalline form.
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Page/Page column 35-36

(2010/04/03)

ETHOXYPHENYLMETHYL INHIBITORS OF SGLT2
The present invention relates to new ethoxyphenylmethyl modulators of SGLT2, pharmaceutical compositions thereof, and methods of use thereof. (Formula I)
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Page/Page column 30

(2010/05/13)

(1 S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio- d -glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment
Derivatives of a novel scaffold, C-phenyl 1-thio-d-glucitol, were prepared and evaluated for sodium-dependent glucose cotransporter (SGLT) 2 and SGLT1 inhibition activities. Optimization of substituents on the aromatic rings afforded five compounds with potent and selective SGLT2 inhibition activities. The compounds were evaluated for in vitro human metabolic stability, human serum protein binding (SPB), and Caco-2 permeability. Of them, (1S)-1,5-anhydro-1-[5- (4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-d-glucitol (3p) exhibited potent SGLT2 inhibition activity (IC50 = 2.26 nM), with 1650-fold selectivity over SGLT1. Compound 3p showed good metabolic stability toward cryo-preserved human hepatic clearance, lower SPB, and moderate Caco-2 permeability. Since 3p should have acceptable human pharmacokinetics (PK) properties, it could be a clinical candidate for treating type 2 diabetes. We observed that compound 3p exhibits a blood glucose lowering effect, excellent urinary glucose excretion properties, and promising PK profiles in animals. Phase II clinical trials of 3p (TS-071) are currently ongoing.
Kakinuma, Hiroyuki,Oi, Takahiro,Hashimoto-Tsuchiya, Yuko,Arai, Masayuki,Kawakita, Yasunori,Fukasawa, Yoshiki,Iida, Izumi,Hagima, Naoko,Takeuchi, Hiroyuki,Chino, Yukihiro,Asami, Jun,Okumura-Kitajima, Lisa,Io, Fusayo,Yamamoto, Daisuke,Miyata, Noriyuki,Takahashi, Teisuke,Uchida, Saeko,Yamamoto, Koji
scheme or table
p. 3247 - 3261
(2010/10/02)

DEUTERATED BENZYLBENZENE DERIVATIVES AND METHODS OF USE
Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions that are affected by SGLT inhibition.
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Page/Page column 89-91

(2010/04/03)

BENZYLBENZENE DERIVATIVES AND METHODS OF USE
Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT inhibition.
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Page/Page column 36-37

(2009/04/25)

Discovery of dapagliflozin: A potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes
The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.
Meng, Wei,Ellsworth, Bruce A.,Nirschl, Alexandra A.,McCann, Peggy J.,Patel, Manorama,Girotra, Ravindar N.,Wu, Gang,Sher, Philip M.,Morrison, Eamonn P.,Biller, Scott A.,Zahler, Robert,Deshpande, Prashant P.,Pullockaran, Annie,Hagan, Deborah L.,Morgan, Nathan,Taylor, Joseph R.,Obermeier, Mary T.,Humphreys, William G.,Khanna, Ashish,Discenza, Lorell,Robertson, James G.,Wang, Aiying,Han, Songping,Wetterau, John R.,Janovitz, Evan B.,Flint, Oliver P.,Whaley, Jean M.,Washburn, William N.
p. 1145 - 1149
(2008/09/20)

Methods of producing C-aryl glucoside SGLT2 inhibitors
Method for the production of C-aryl glucoside SGLT2 inhibitors useful for the treatment of diabetes and related diseases. and intermediates thereof. The C-aryl glucosides may be complexed with amino acid complex forming reagents.
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Page 18

(2010/02/07)

C-aryl glucoside SGLT2 inhibitors and method
An SGLT2 inhibiting compound is provided having the formula A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.
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(2008/06/13)

C-aryl glucoside SGLT2 inhibitors and method
An SGLT2 inhibiting compound is provided having the formula A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.
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(2008/06/13)