21187-98-4Relevant articles and documents
Synthesis and characterization of novel oxime prodrug of G liclizide
Vijayaraj,Anitha,Omshanthi,Sampath Kumar
, p. 6989 - 6992 (2014)
Diabetes has emerged as a major healthcare problem throughout the world. Gliclizide is a widely used sulphonyl urea compound to treat diabetes. Gliclizide is categorized under biopharmaceutical classification system class II drug which do have poor solubility. Drug molecules with limited aqueous solubility are becoming increasingly prevalent in the research and development portfolios of discovery focused pharmaceutical companies. Prodrugs are an established concept to overcome barriers like poor solubility. Aqueous solubility is an important parameter to enhance the bioavailability of drug. Hence the present study aims to enhance aqueous solubility and in turn bioavailability by synthesis of novel oxime prodrug of gliclizide. The prepared prodrug was characterized by IR, NMR, Mass and DSC. in vitro chemical hydrolysis profiles revealed that the synthesized oxime derivatives of gliclizide are chemically stable in simulated gastric fluid pH 1.2. Decrease in log P value indicates the increase in hydrophilic property of synthesized oxime derivatives of gliclizide.
Sulfonylurea compound synthesis method
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Paragraph 0028; 0056-0067, (2021/11/26)
The invention discloses a sulfonylurea compound synthesis method, which comprises: respectively dissolving p-toluenesulfonyl isocyanate and an amino compound in an organic solvent to obtain a p-toluenesulfonyl isocyanate organic solution and an amino compound organic solution; under the protection of nitrogen and/or inert gas, dropwise adding the amino compound organic solution into the p-toluenesulfonyl isocyanate organic solution for reaction; and after the reaction is finished, carrying out rotary evaporation to remove the solvent, and removing impurities to obtain the sulfonylurea compound. According to the synthesis method, the sulfonylurea compound can be prepared at the room temperature through specific raw material selection, energy consumption is reduced, meanwhile, the synthesis method is easy to operate, the synthesized product is easy to separate, and the purity of the product is high.
Rapid Multigram-Scale End-to-End Continuous-Flow Synthesis of Sulfonylurea Antidiabetes Drugs: Gliclazide, Chlorpropamide, and Tolbutamide
Sagandira, Cloudius R.,Watts, Paul
supporting information, (2021/12/02)
A multigram-scale robust, efficient, and safe end-to-end continuous-flow process for the diabetes sulfonylurea drugs gliclazide, chlorpropamide, and tolbutamide is reported. The drugs were prepared by the treatment of an amine with a haloformate affording carbamate, which was subsequently treated with a sulfonamide to afford sulfonylurea. Gliclazide was obtained in 87% yield within 2.5 minutes total residence time with 26 g/h throughput; 0.2 kg of the drug was produced in 8 hours of running the system continuously. Chlorpropamide and tolbutamide were both obtained in 94% yield within 1 minute residence time with 184-188 g/h throughput; 1.4-1.5 kg of the drugs was produced in 8 hours of running the system continuously. N-Substituted carbamates were used as safe alternatives to the hazardous isocyanates in constructing the sulfonyl urea moiety.
Preparation method of gliclazide
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, (2021/10/27)
The invention relates to the field of medicine synthesis, in particular to a preparation method of gliclazide and an intermediate of gliclazide. The preparation method comprises a Mannich reaction, an amino protection reaction, a Perkin reaction, an epoxidation reaction, a hydrolysis reaction, a decarboxylation reaction and a reductive amination reaction. The preparation method is mild in reaction condition, green and environment-friendly, few three wastes are generated, a high-risk reducing agent does not need to be used, nitrosation reaction does not need to be carried out, and introduction of nitroso-nitroso impurities is successfully avoided.
A novel and facile process for the synthesis of gliclazide
Ambulgekar, Girish V.,Dhake, Vilas,Kumar, Pramod,Reddy, Muchumarri R.,Hattali, Jakraya
, p. 760 - 765 (2018/09/26)
Background: Gliclazide is a second generation sulfonyl urea which acts as hypoglycemic agent (oral antidiabetic agent). It improves the function of blood coagulation, has hypoglycemic effect, and thus has been widely used in clinical treatment. Several syntheses of Gliclazide have been reported, but all of them have some drawbacks. Therefore, there has been an ever-increasing interest in finding a novel route for Gliclazide using simple and easily commercial available chemicals. Methods: A Novel and facile process of preparing Gliclazide is herein reported which is comprised of three steps. Aryl haloformate was reacted with amino heterocyclic compound to give carbamate. The salt of p-toluene sulfonamide was prepared with metal hydroxide or metal alkoxide, and this salt of sulfonamide was then reacted with carbamate to give Gliclazide. Results: The carbamate produced from aryl haloformates was reacted with salt of p-toluene sulfonamide in the presence of base to produce Gliclazide with good yield and purity. The salt of p-toluene sulfonamide was prepared by two methods. In one method, salt was prepared using base at 100o C in polar aprotic solvent which was reacted with carbamate at 25o C to give Gliclazide. This method gives 70% yield of Gliclazide with purity above 99%. In another method, the salt of p-toluene sulfonamide was prepared at 100o C in polar aprotic solvent using base. The salt was isolated. The isolated salt of sulfonamide is stable at 25o C. This salt was reacted with carbamate at 25o C to give Gliclazide. This method gives 64% yield of Gliclazide with purity above 99%. The various solvents, bases were tested in this investigation. It was observed that excellent yield of the product was obtained when the reaction was carried out by using DMSO as solvent and potassium tert-butoxide as base. Conclusion: In conclusion, we have developed new and effective process for the synthesis of Gliclazide via condensation of sulfonamide with various carbamates using a less expensive aryl haloformates with good yield and purity.
Preparation method of gliclazide side chain and preparation method of gliclazide
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, (2017/07/04)
The invention relates to a preparation method of N-amino-3-azabicyalo [3.3.0] octane serving as a gliclazide side chain. The gliclazide side chain is obtained by carrying out one-step hydrogenation reduction on N-cyclopentyl amine imide through a transition metal atom-modified ruthenium-carbon catalyst. The activity of the modified ruthenium-carbon catalyst used in the method is obviously higher than that of an existing commercial ruthenium-carbon catalyst, so that the imide hydrogenation reaction which is hard to realize in the N-cyclopentyl amine imide can be carried out successfully. The preparation method of the gliclazide side chain is safe, efficient, high in yield and simple for posttreatment; the catalyst can be cyclically used indiscriminately, so that the production cost is substantially reduced, and green synthesis is basically realized; no waste water and no waste slag are produced; and the preparation method is particularly suitable for large-scale industrial production. The invention further relates to a production method of gliclazide, which has the advantages of short synthesis path, high yield, low preparation cost and the like.
Preparation method of gliclazide in green synthesis technology
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, (2017/08/29)
The present invention provides a gliclazide green synthesis process which is simple in process, safe and environmentally-friendly, and convenient to actually operate, N-amino-1, 2-cyclohexane dicarboximide is used as a raw material, the gliclazide green synthesis process mainly includes the following steps: N-amino-3-azabicyalo[3, 3, 0] octane is prepared by high pressure hydrogenation of the N-amino-1, 2-cyclohexane dicarboximide, the N-amino-3-azabicyalo[3, 3, 0] octane is reacted with phosgene in high pressure conditions to prepare N-(hexahydrocyclopentadiene[c] pyrrole-2(1H)-yl)-amino chloride, and finally gliclazide prepared by condensation reaction of the N-(hexahydrocyclopentadiene[c] pyrrole-2(1H)-yl)-amino chloride and para toluene sulfonamide.
USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS
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, (2008/06/13)
The present invention relates to the use of a substituted 2-phenylbenzimidazole of formula I wherein R1, R2, R3, R 4, R5 and m have the meanings given in the claims, for the preparation of a medicament for the treatment or prevention of diseases involving glucagon receptors, as well as new compounds of formula I wherein R1 is a group of formula
Combinations comprising dipeptidylpeptidase-iv inhibitor
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, (2008/06/13)
The invention relates to a combination which comprises a DPP-IV inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6-phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers, α-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and α2-adrenergic antagonists, for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more especially type 2 diabetes mellitus, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; and the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight.
