33288-71-0Relevant articles and documents
The physico‐chemical properties of glipizide: New findings
Berbenni, Vittorio,Bruni, Giovanna,Capsoni, Doretta,Cardini, Andrea,Ghione, Ines,Girella, Alessandro,Marini, Amedeo,Milanese, Chiara
, (2021)
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.
Synthesis and evaluation of α-glucosidase inhibitory activity of sulfonylurea derivatives
Bui, Thi Thoi,Tran, Van Loc,Ngo, Dai Quang,Tran, Van Chien,Tran, Van Sung,Tran, Thi Phuong Thao
, p. 163 - 171 (2021/03/16)
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.
Preparation method of glipizide intermediates
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Paragraph 0044; 0045; 0052; 0054, (2018/03/26)
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.
