- The structure of glibenclamide in the solid state
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The structure of glibenclamide, 5-chloro-N-(2-{4-[(cyclohexylamino) carbonyl] aminosulfonyl}phenyl) ethyl)-2-methoxybenzamide, an important antidiabetic drug, has been studied both in solution and in the solid state by a combination of NMR spectroscopy and theoretical calculations. The possibility that glibenclamide suffers a tautomerization under melting to afford a desmotrope was rejected. Copyright
- Sanz, Dionisia,Claramunt, Rosa M.,Alkorta, Ibon,Sanchez-Sanz, Goar,Elguero, Jose
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- Total Synthesis of Glipizide and Glibenclamide in Continuous Flow
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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.
- Sagandira, Cloudius R.,Khasipo, Agnes Z.,Watts, Paul
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supporting information
p. 16028 - 16035
(2021/10/14)
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- Direct Amidation of Carboxylic Acids through an Active α-Acyl Enol Ester Intermediate
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The development of a highly efficient and simple protocol for the direct amidation of carboxylic acids is described employing ynoates as novel coupling reagents. The transformation proceeds in good to excellent yields via in situ α-acyl enol ester intermediates formation under mild reaction conditions. This useful method has been demonstrated for a range of substrates to provide a succinct access to structurally diverse amides, including key intermediates of glibenclamide, tiapride hydrochloride, and nateglinide, and can be conducted on a mole scale.
- Xu, Xianjun,Feng, Huangdi,Huang, Liliang,Liu, Xiaohui
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p. 7962 - 7969
(2018/06/18)
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- Synthesis method of glibenclamide
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The invention discloses a synthesis method of glibenclamide, which includes the steps of: 1) protection of amino groups with trichloroacetic anhydride; 2) sulfonation; 3) sulfo-amidation; 4) amidation: performing a reaction to 5-chloro-2-methoxybenzoic acid with N,N-carbonyl diimidazole and performing a reaction to the product with a compound (III) under effect of a second acid-binding agent; 5) addition: adding the second acid-binding agent and crown ether, in catalytic amount, to perform an addition reaction to a compound (IV) with cyclohexyl isocyanate to prepare the glibenclamide. The method is high in yields in all steps, wherein residue of impurities is effectively reduced during processes of protection, deprotection, acid treatment, alkali treatment and water-adding separation of the substrate. According to the method, a phase-transfer catalyst is matched with the second acid-binding agent, so that compatibility between the isocyanate and the compound (IV) is effectively increased, and the nucleophilic reaction is carried out more completely. The produced product is higher in purity.
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- Synthetic process of 4-[2-(5-chloro-2-methoxy benzamide)ethyl]benzsulfamide
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The invention discloses a synthetic process of 4-[2-(5-chloro-2-methoxy benzamide)ethyl]benzsulfamide, and belongs to the technical field of medicinal synthesis processes. According to the process, 5-chloro-2-methoxybenzoic acid and phenylethylamine serve as the raw materials, and a target product is obtained through reactions of four steps including acylating chlorination, amidation, chlor amidation osulfonation and sulfanil amination. By means of the synthesis method, low-price industrial chemicals serve as raw materials and reaction reagents, single-solvent systems are adopted, smooth process connection is achieved, reaction yield is increased, process operation is simplified, and production cost is reduced while raw material cost is reduced.
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- Design and Performance Validation of a Conductively Heated Sealed-Vessel Reactor for Organic Synthesis
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A newly designed robust and safe laboratory scale reactor for syntheses under sealed-vessel conditions at 250 °C maximum temperature and 20 bar maximum pressure is presented. The reactor employs conductive heating of a sealed glass vessel via a stainless steel heating jacket and implements both online temperature and pressure monitoring in addition to magnetic stirring. Reactions are performed in 10 mL borosilicate vials that are sealed with a silicone cap and Teflon septum and allow syntheses to be performed on a 2-6 mL scale. This conductively heated reactor is compared to a standard single-mode sealed-vessel microwave instrument with respect to heating and cooling performance, stirring efficiency, and temperature and pressure control. Importantly, comparison of the reaction outcome for a number of different synthetic transformations performed side by side in the new device and a standard microwave reactor suggest that results obtained using microwave conditions can be readily mimicked in the operationally much simpler and smaller conventionally heated device.
- Obermayer, David,Znidar, Desiree,Glotz, Gabriel,Stadler, Alexander,Dallinger, Doris,Oliver Kappe
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p. 11788 - 11801
(2016/12/09)
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- CRYOPYRIN INHIBITORS FOR PREVENTING AND TREATING INFLAMMATION
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Inhibitors that are anti-inflammatory agents are provided, as are methods of using the analogs to inhibit inflammation and prevent or treat diseases and conditions associated with inflammation, such as heart failure and autoimmune diseases.
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Page/Page column 21; 23; title; sheet 3
(2014/12/12)
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- Mechanosynthesis of pharmaceutically relevant sulfonyl-(thio)ureas
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We demonstrate the first application of mechanochemistry to conduct the synthesis of sulfonyl-(thio)ureas, including known anti-diabetic drugs tolbutamide, chlorpropamide and glibenclamide, in good to excellent isolated yields by either stoichiometric base-assisted or copper-catalysed coupling of sulfonamides and iso(thio)cyanates. the Partner Organisations 2014.
- Tan, Davin,?trukil, Vjekoslav,Mottillo, Cristina,Fri??i?, Tomislav
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p. 5248 - 5250
(2014/05/06)
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- Investigation of structure-activity relationships in a series of glibenclamide analogues
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In this study, the synthesis of 15 new glibenclamide analogues is described. The conformational trends of these analogues were investigated using Monte Carlo conformational analysis. The conformational analysis results resolved the discrepancy between previous molecular modelling simulations of glibenclamide and allowed rationalizing the effect of aqueous environment on the overall conformation. The 3D-QSAR study was carried out with respect to the compounds' ability to antagonize the [3H]-glibenclamide binging in rat cerebral cortex. Superimposition of the antagonists was performed using the conformations derived from atom-by-atom fit to the glibenclamide crystal structure and this alignment was used to develop CoMFA models. CoMFA provided a good predictability: number of PLS components = 2, q2 = 0.876, R 2 = 0.921, SEE = 0.455 and F = 70. Best CoMFA models showed the steric and lipophilic properties as the major interacting forces whilst the electrostatic property contribution was a minor factor.
- Yuriev, Elizabeth,Kong, David C.M.,Iskander, Magdy N.
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p. 835 - 847
(2007/10/03)
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- Process for preparing p-(5-chloro-2-methoxy-benzamidoethyl)-benzene sulfonamide
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A process for preparing p-[5-chloro-2-methoxy-benzamidoethyl]-benzene sulfonamide consisting of treating 5-chlorosalicylic acid or its ester by methylating and aminolysis to form N-phenethyl-5-chloro-2-methoxybenzamide followed by chlorosulfonation and aminolysis.
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