33288-71-0

Usage

Uses

Used in Pharmaceutical Industry:
2-[4-Aminosulfonyl-phenyl]-ethyl-5-methylpyrazinecarboxamide is used as an intermediate in the synthesis of Glipizide (G410225) for its role in the development of medications for diabetes management. As a key component in the production of Glipizide, it contributes to the creation of drugs that help regulate blood sugar levels in patients with type 2 diabetes.
Used in Chemical Synthesis:
In the field of chemical synthesis, 2-[4-Aminosulfonyl-phenyl]-ethyl-5-methylpyrazinecarboxamide is utilized as a building block for the development of other complex molecules and compounds. Its unique structure allows for further reactions and modifications, potentially leading to the discovery of new pharmaceuticals or chemical products with various applications.

InChI:InChI=1/C14H16N4O3S/c1-10-8-18-13(9-17-10)14(19)16-7-6-11-2-4-12(5-3-11)22(15,20)21/h2-5,8-9H,6-7H2,1H3,(H,16,19)(H2,15,20,21)

Upstream product

• 29094-61-9 glipizide 
• 50886-34-5 5-methylpyrazine-2-carbonyl chloride 
• 35303-76-5 4-(2-aminoethyl)benzenesulfonamide 
• 5521-55-1 2-methylpyrazin-5-carboxylic acid 
• 2015-16-9 N-(4-[2-amino-ethyl]-benzenesulfonyl)-N'-cyclohexyl urea 
• 258262-54-3 tert-butyl (4-sulfamoyl phenethyl)carbamate 

Downstream Products

• 1076198-09-8 ethyl ({4-[2-(5-methylpyrazine-2-carboxamido)ethyl]phenyl}sulfonyl)carbamate 
• 29094-61-9 glipizide 

Relevant academic research and scientific papers

The physico‐chemical properties of glipizide: New findings

The present work is a concrete example of how physico‐chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X‐ray powder diffraction (XRPD), FT‐IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5‐methyl‐N‐[2‐(4‐sulphamoylphenyl) ethyl] pyrazine‐2‐carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT‐IR and XRPD led to identifying a new polymorphic form of 5‐methyl‐N‐[2‐(4‐sulphamoylphenyl) ethyl] pyrazine‐2‐carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.

Total Synthesis of Glipizide and Glibenclamide in Continuous Flow

Glipizide and glibenclamide remain some of the widely prescribed antidiabetic sulfonylurea drugs for the treatment of type 2 diabetes mellitus. Herein the authors report on an isocyanate-free synthetic procedure towards the preparation of these on demand drugs at multigram scale using continuous flow technology. The safety concern over the use of isocyanates in most of the existing synthetic routes was dealt with in this present work by using N-carbamates synthesised in situ from activation of amines with chloroformates as safer alternatives. An overall yield of 80–85 % was obtained for the semi-telescoped steps within 10 min total residence time.

Synthesis and evaluation of α-glucosidase inhibitory activity of sulfonylurea derivatives

Two series of sulfonylureas derivatives including 24 compounds (4, 7, 5a-5o, 8a-8h), among them 17 new derivatives, have been synthesized and evaluated for their α-glucosidase inhibitory activity. Compounds 5c, 5h and 8e showed significant in vitro α-glucosidase inhibition with IC50 values of 5.58, 79.85 and 213.36 μm, respectively, comparing with the standard compounds acarbose (IC50 = 268.29 μm) and glipizide (IC50 = 300.47 μm). The preliminary structure-activity relationships (SARs) of the synthesized compounds were also investigated.

NOVEL COMPOUNDS AND USES

The present invention relates to compounds of formula (I): wherein Q is O or S; R1 is a cyclic group substituted with at least one group X, wherein R1 may optionally be further substituted; X is any group comprising a carbonyl group; and R2 is a cyclic group substituted at the α-position, wherein R2 may optionally be further substituted. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the dual action of NLRP3 inhibition and the stimulation of insulin secretion.

Preparation method of glipizide intermediates

The invention discloses a preparation method of glipizide intermediates. The method comprises the steps that N,N'-carbonyldiimidazole is dissolved in N,N-dimethylformamide for being used as a condensing agent, 5-methyl-pyrazine-2-carboxylic acid is dissolved in N,N-dimethylformamide, and the N,N-dimethylformamide solution of N,N'-carbonyldiimidazole is dropwise added at 45 DEG C to generate a active intermediate 5-methyl-pyrazine-2-carbonylimidazole, after cooling, the 5-methyl-pyrazine-2-carbonylimidazole is subjected to condensation together with 4-(2-aminoethyl) benzene sulfonamide, and theglipizide intermediates are obtained. The preparation method of the invention has the advantages of easy operation and low cost, is suitable for high-volume industrial production; post-processing chromatographic purity can be up to 99.0% or above, and the yield is up to 90% or above. In addition, the preparation method has mild reaction conditions, high yield and high product purity, and is moresuitable for industrialized production.

Preparation method of 2-[4-aminosulfonyl-phenyl]-ethyl-5-methylpyrazine formamide

The invention provides a preparation method of 2-[4-aminosulfonyl-phenyl]-ethyl-5-methylpyrazine formamide. The preparation method comprises the following steps: step one, taking 5-methylpyrazine-2-carboxylic acid as the primary raw material, and reacting 5-methylpyrazine-2-carboxylic acid with sulfoxide chloride to generate an intermediate (I); step two, reacting the intermediate (I) obtained in the step one with p-aminobenzenesulfonamide and triethylamine in dichloromethane to generate a crude product of 2-[4-aminosulfonyl-phenyl]-ethyl-5-methylpyrazine formamide; and step three, washing the crude product obtained in the step two, and removing impurities from the crude product to obtain a finished product of 2-[4-aminosulfonyl-phenyl]-ethyl-5-methylpyrazine formamide. On the basis that the product yield and quality are not influenced, strongly toxic ethyl chloroformate is not used, and thus the safety is improved. The refluxing temperature of sulfoxide chloride is low, and the refluxing time is short. The reactions are carried out at a room temperature, the requirement on reaction conditions is low, and the reaction conditions are easy to realize therefore.

Sulfonylureas as Concomitant Insulin Secretagogues and NLRP3 Inflammasome Inhibitors

Insulin-secretory sulfonylureas are widely used, cost-effective treatments for type 2 diabetes (T2D). However, pancreatic β-cells are continually depleted as T2D progresses, thereby rendering the sulfonylurea drug class ineffective in controlling glycaemia. Dysregulation of the innate immune system via activation of the NLRP3 inflammasome, and the consequent production of interleukin-1β, has been linked to pancreatic β-cell death and multiple inflammatory complications of T2D disease. One proposed strategy for treating T2D is the use of sulfonylurea insulin secretagogues that are also NLRP3 inhibitors. We report the synthesis and biological evaluation of nine sulfonylureas that inhibit NLRP3 activation in murine bone-marrow- derived macrophages in a potent, dose-dependent manner. Six of these compounds inhibited NLRP3 at nanomolar concentrations and can also stimulate insulin secretion from a murine pancreatic cell line (MIN6). These novel compounds possess unprecedented dual modes of action, paving the way for a new generation of sulfonylureas that may be useful as therapeutic candidates and/or tool compounds in T2D and its associated inflammatory complications.

Diethylenetriamine-Mediated Direct Cleavage of Unactivated Carbamates and Ureas

Diethylenetriamine is effective for the direct cleavage of unactivated carbamates and ureas without additional reagents and catalysts. Various carbamates and ureas were cleaved to afford products in good yield, and the reactions were not affected by air or moisture. Unique chemoselective cleavage of carbamate and urea in the presence of amides was also achieved.

Process for the preparation of N-[2-[4-(aminosulfonyl) phenyl]ethyl]5-methylpyrazinecarboxamide

A process for the preparation of N-[2-[4-(amino-sulfonyl)phenyl]ethyl]-5-methylpyrazinecarboxamide is described which is simple and effective.