35 results about "SGLT Inhibitors" patented technology

The present invention is directed to a novel process for the preparation of compounds having inhibitory activity against sodium-dependent glucose transporter (SGLT) being present in the intestine or kidney.

The present invention is directed to a novel process for the preparation of compounds having inhibitory activity against sodium-dependent glucose transporter (SGLT) being present in the intestine or kidney.

Novel indole derivatives of formula (I) or a pharmaceutically acceptable salt thereof:

wherein R¹ is fluorine, or chlorine, and R² is hydrogen, or fluorine, which are SGLT inhibitors and are useful for treatment or prevention of diabetes and related conditions.

The invention belongs to the field of marine medicine, and particularly relates to an application of oligosaccharides containing D-galactose and L-galactose and derivatives of the oligosaccharides asa sodium-glucose cotransporter (SGLT) inhibitor. The galactooligosaccharides and derivatives are prepared by the following steps: by using red algae polysaccharide containing the D-/L-galactose as a raw material, performing degradation by using a physical method, a chemical method, a bioenzyme method or any combination of the above methods to prepare the galactooligosaccharides and the derivativesof the galactooligosaccharides with different degrees of polymerization, wherein the molecular skeleton contains the D-galactose and the L-galactose and derivatives thereof. The raw material of the product provided by the invention is from the red algae polysaccharide, and has the advantages of rich resources, a simple preparation process, high safety, clear targets and easy industrialization, the oligosaccharides and the derivatives are used as the SGLT1 and 2 inhibitor, and has broad application prospects in the development of medicines for treating diseases such as diabetes mellitus, obesity, diabetic nephropathy and glucose and lipid metabolism disorder and functional foods for improving non-alcoholic fatty liver diseases.

The invention relates to a C-aryl glucoside derivative, as well as a medical composition, a preparation method and application thereof. The preparation method comprises the following steps of: method I, in a solvent, under the action of alkali, performing a deacetylation protecting group reaction on compounds 1-f; method II: 1, performing a Mitsunobu reaction on components 2-g and (as shown in the description); and 2, performing a deacetylation protecting group reaction on the compounds 2-f obtained in the step 1; and method III: 1, mixing compounds 3-g and (as shown in the description), and performing a nucleophilic substitution reaction; and 2, performing a deacetylation protecting group reaction on the compounds 3-f obtained in the step 1. The medical composition comprises the C-aryl glucoside derivative, salt and/or prodrug of the C-aryl glucoside derivative which are/is acceptable in pharmacy, and auxiliary materials. The invention further relates to the C- aryl glucoside derivative, and application of salt or medical compositions of the C- aryl glucoside derivative, which is acceptable in pharmacy, for preparing SGLT inhibitors. The C- aryl glucoside derivative disclosed by the invention provides a new direction for research of the SGLT inhibitors. (As shown in the description)

The present invention relates to novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to the processes for the synthesis of novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention also provides pharmaceutical compositions comprising novel compounds of Formula I and methods of treating or preventing one or more conditions or diseases that may be regulated or normalized via inhibition of Sodium Glucose Cotransporter-2 (SGLT-2).

The present invention relates to novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to the processes for the synthesis of novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention also provides pharmaceutical compositions comprising novel compounds of Formula I and methods of treating or preventing one or more conditions or diseases that may be regulated or normalized via inhibition of Sodium Glucose Cotransporter-2 (SGLT-2).

The present invention relates to combination therapy comprising a DPP4 inhibitor and an SGLT inhibitor. The combination of the present invention leads to increase plasma GLP-1 level and the combination is useful for prevention or treatment of conditions such as diabetes and diseases related to diabetes.

Radiolabeled tracers for binding to sodium/glucose cotransporters (SGLTs), and their synthesis, are provided. The tracers are high-affinity inhibitors of SGLTs, glycosides labeled with radioactive halogens. Also provided are in vivo and in vitro techniques for using the tracers as analytical tools to study the biodistribution and regulation of SGLTs in health and disease, and to evaluate therapeutic interventions. The ability to monitor radiolabel tracer disposition in real time enables the design of new SGLT inhibitors with lower metabolism and higher efficiency.

Provided herein are methods of managing feline diabetes, said methods include administering to a feline in need thereof a total daily dosage of about 5 to 50 mg of Compound 1, having the formula:

or a pharmaceutically acceptable form thereof. Also provided herein are methods of managing feline diabetes by administering to a feline in need thereof an effective amount of a SGLT inhibitor, wherein said effective amount is no more than 10 to 30% of the dose required to produce an elevated frequency of diarrhea or loose stool in a healthy feline.

The invention discloses a method for preparing a compound 1 and a compound 2, the structure of the compound 1 and the structure of the compound 2 are shown in the specification.The method comprises the following steps: 1) carrying out selective dibromination on 2, 3-dihydrobenzofuran-7-aniline serving as a raw material by using a bromination reagent to obtain 4, 6-dibromo-2, 3-dihydrobenzofuran-7-aniline; 2) subjecting the 4, 6-dibromo-2, 3-dihydrobenzofuran-7-aniline obtained in the step 1) to a Sandmeyer reaction for chlorination to give 4, 6-dibromo-7-chloro-2, 3-dihydrobenzofuran; 3-1) performing selective bromine removal on the 4, 6-dibromo-7-chloro-2, 3-dihydrobenzofuran obtained in the step 2) by using a strong base, adding a formylation reagent to give the compound 1; and 3-2) performing selective bromine removal on the 4, 6-dibromo-7-chloro-2, 3-dihydrobenzofuran obtained in the step 2) by using a strong base and then reacting with 4-cyclopropylbenzaldehyde to give the compound 2.

The invention relates to a SGLTs (sodium-dependent glucose transporters 2) inhibitor with a structure as shown in a formula (I), a preparation method thereof and a pharmaceutical application of the inhibitor. The series compound can be widely applied to treatment of diseases such as diabetes, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, insulin resistance, hyperglycemia, hyperinsulinemia, elevated level of fatty acid or glycerol, hyperlipemia, obesity, hypertriglyceridemia, X syndrome, diabetic complications or atherosclerosis or hypertension, and can be hopefully developedinto a new-generation SGLTs inhibitor.

The invention relates to the technical field of medicines, and particularly discloses a composition, application thereof and a medicine. The composition comprises an SGLT inhibitor and a tyrosine kinase activity inhibitor. The present invention provides a composition containing an SGLT inhibitor and a tyrosine kinase activity inhibitor. Based on the inhibition effect of TKI on tyrosine kinase of receptors such as VEGFR (vascular endothelial growth factor receptor), EGFR (epidermal growth factor receptor), HER2 (human epidermal growth factor receptor 2) and the like, an in-vitro anti-tumor test shows that SGLT inhibitors such as sofogliflozin, SY-009, Licogliflozin and the like can generate a synergistic inhibition effect on tumors when being combined with a tyrosine kinase activity inhibitor; in addition, the curative effect of TKI drugs can be remarkably enhanced, the drug resistance can be reversed, and the compound can be used for cancer treatment and preparation of anti-cancer drugs.

Compounds as dual SGLT1/SGLT2 inhibitors, and use in the preparation of medicaments as dual SGLT1/SGLT2 inhibitors. The compound is a compound represented by formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof.

The invention relates to a preparation method of an SGLTs inhibitor and a key intermediate of the SGLTs inhibitor. The SGLTs inhibitor is (1S, 2S, 3S, 4R, 5S)-5-(3-((2, 3-dihydrobenzo [b] [1, 4] dioxin-6-yl)methyl)-4-ethyl phenyl)-1-(hydroxymethyl)-6, 8-dioxabicyclo [3.2.1] octane-2, 3, 4-triol. According to the preparation method, 6-(2-ethyl-5-iodobenzyl)-2, 3-dihydrobenzo [b] [1, 4] dioxin is taken as a raw material, silyl is taken as a protecting group, and six-step reaction is carried out to prepare the product. The preparation method disclosed by the invention is simple to operate, high in yield of each step and stable in process, can adapt to industrial production requirements, solves the problem of drug accessibility, and is beneficial to acceleration of clinical development of the SGLTs inhibitor and drug marketing.

Presented here are methods using alpha-methylglucoside (AMG) in vivo as an indicator for glucose absorption from the gastrointestinal (GI) system or glucose excretion in the urine after oral administration of AMG. The methods find use in, for example, but not limited to, determining the effect of a sodium-dependent glucose transporter (SGLT) inhibitor in an animal, comparing the differences in the effects of a first and second SGLT inhibitor in an animal, and diagnosing a disease associated with glucose absorption from the gastrointestinal (GI) system or glucose excretion from the kidney in an animal.

Disclosed are an amine solvate of a sodium-glucose linked transporter (SGLT) inhibitor, and a preparation method and application thereof. The SGLT inhibitor is (1S,2S,3S,4R,5S)-5-(3-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-4-ethylbenzyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol. Further provided is a crystalline compound of the amine solvate, a pharmaceutical composition comprising the amine solvate, and an application of the amine solvate in preparing an SGLT-inhibiting pharmaceutical product.

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.

The present invention relates to a method for producing an intermediate useful for the synthesis of a diphenylmethane derivative that can be used as a SGLT inhibitor. A method for synthesizing a compound of formula 7 according to the present invention has solved the problem of an existing synthesis process which requires an additional process due to the synthesis of Grignard reagent and the management of a related substance. In addition, the process can be simplified by minimizing the formation of the related substance and eliminating the need for reprocessing of reaction products, thereby becoming capable of maximizing a yield of a diphenylmethane derivative.

A pyranoglucose-substituted pyrazole compound, used as a pharmaceutical intermediate, having the structural formula represented by formula (9c). The present invention further relates to an intermediate compound represented by formula (10c) or a salt thereof. The present invention further relates to a preparation method of the aforementioned intermediate compound and a method of using the same to prepare an SGLT inhibitor. By means of the novel key intermediate, the preparation technique of an SGLT inhibitor is greatly simplified. In addition, because the intermediate can be precipitated in the form of a salt and is easy to purify, the purity of the SGLT inhibitor is significantly increased, compared with the original preparation pathway (crude product purity can reach 99% or more). (I)