664-95-9Relevant articles and documents
A facile synthesis of sulfonylureas: Via water assisted preparation of carbamates
Tanwar, Dinesh Kumar,Ratan, Anjali,Gill, Manjinder Singh
, p. 4992 - 4999 (2017/07/11)
A novel and simple approach to the synthesis of sulfonylureas has been reported. It involved the reaction of various amines with diphenyl carbonate to yield the corresponding carbamates, which subsequently reacted with different sulphonamides to produce different sulfonylureas in excellent yields. The first reaction of diphenyl carbonate with amines was carried out in aqueous:organic (H2O:THF, 90:10) medium at room temperature to produce carbamates that paved a straightforward route to sulfonylureas after reaction with sulfonamides. The above process avoided traditional multistep protocols and the use of hazardous, irritant, toxic and moisture sensitive reagents such as phosgene, isocyanates and/or chloroformates.
Design and development of sulfonylurea derivatives as zinc metalloenzyme modulators
Hadianawala, Murtuza,Datta, Bhaskar
, p. 8923 - 8929 (2016/02/05)
Sulfonamide derivatives are an important class of zinc metalloenzyme inhibitors. While the sulfonylurea group is a bioisoster of sulfonamide, their effect on the modulation of metalloenzymes has never been studied. In the present work we synthesize and screen new sulfonylurea derivatives towards the zinc metalloenzymes, human Carbonic Anhydrase II (hCA II) and histone deacetylase 1 (HDAC 1). Specific sulfonylurea derivatives are found to inhibit hCA II with IC50 in the nano molar to micro molar range. Docking studies indicate the binding of the inhibitors to the mouth of the active site cavity thereby blocking access to the enzyme. Surprisingly sulfonylurea derivatives exhibit activation of HDAC 1 rather than inhibition. The activation of HDAC 1 is not uniform across the derivatives tested suggesting a specific mode that depends on structural features of the compounds. Extensive research has been performed on HDAC inhibitors due to their potential as anti-cancer agents, however relatively little has been reported in terms of HDAC activation. In this work, we present the distinctly divergent behavior of the same class of molecules namely sulfonylurea derivatives with respect to hCA II and HDAC 1 and attempt to provide an understanding of the same.
Mechanosynthesis of pharmaceutically relevant sulfonyl-(thio)ureas
Tan, Davin,?trukil, Vjekoslav,Mottillo, Cristina,Fri??i?, Tomislav
supporting information, p. 5248 - 5250 (2014/05/06)
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.
Synthesis, characterization and DNA-binding studies of 1-cyclohexyl-3-tosylurea and its Ni(II), and Cd(II) complexes
Xi, Pin-xian,Xu, Zhi-hong,Liu, Xiao-hui,Cheng, Feng-juan,Zeng, Zheng-zhi
experimental part, p. 523 - 528 (2009/02/06)
1-Cyclohexyl-3-tosylurea (HL) and its two complexes, ML2·2H2O [M{double bond, long}Ni(1), and Cd(2)], have been synthesized and characterized on the basis of elemental analyses, molar conductivities, IR spectra and thermal analyses. In addition, the DNA-binding properties of the ligand and the two complexes have been investigated by electronic absorption, fluorescence, CD spectroscopy and viscosity measurements. The experiment results suggest that the ligand and its two complexes bind to DNA via a groove binding mode, and the binding affinity of the complex 2 is higher than that of the complex 1 and the ligand.
Synthesis, characterization, antioxidant activity, and DNA-binding studies of 1-cyclohexyl-3-tosylurea and its Nd(III), Eu(III) complexes
Xi, Pin-Xian,Xu, Zhi-Hong,Liu, Xiao-Hui,Chen, Feng-Juan,Huang, Liang,Zeng, Zheng-Zhi
experimental part, p. 541 - 546 (2009/04/11)
A new ligand, 1-cyclohexyl-3-tosylurea (H2L), was prepared by condensation ethyl N-(3-tossulfonyl) carbamate and cyclohexanamine. Its two lanthanide(III) complexes, Ln(H2L)3·3NO3 [Ln=Nd (1), and Eu (2)], have been synthesized and characterized on the base of element analyses, ESI-MS, molar conductivities, IR spectra and thermogravimetry/differential thermal analysis (TG-DTA). In addition, the DNA-binding properties of the ligand and its complexes have been investigated by electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroic (CD) spectroscopy and viscosity measurements. The experiment results suggest that the ligand and its two complexes bind to DNA via a groove binding mode, and the binding affinity of the complex 2 is higher than that of the complex 1 and the ligand. Furthermore, the antioxidant activity (superoxide and hydroxyl radical) of the ligand and its metal complexes was determined by using spectrophotometer methods in vitro. These complexes were found to possess potent antioxidant activity and be better than standard antioxidants like vitamin C and mannitol. In particular, complex 2 displayed excellent activity on the superoxide and hydroxyl radical.
Investigation of structure-activity relationships in a series of glibenclamide analogues
Yuriev, Elizabeth,Kong, David C.M.,Iskander, Magdy N.
, p. 835 - 847 (2007/10/03)
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.
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.
Scavenge-ROMP-filter: a facile strategy for soluble scavenging via norbornenyl tagging of electrophilic Reagents.
Moore, Joel D,Harned, Andrew M,Henle, Julia,Flynn, Daniel L,Hanson, Paul R
, p. 1847 - 1849 (2007/10/03)
[reaction: see text] A new "chemical tagging" method for homogeneous electrophilic scavenging is described. The method utilizes 5-norbornene-2-methanol to scavenge/tag a variety of electrophiles that are present in excess. Once tagging is complete, the crude reaction mixture is subjected to a rapid ROM polymerization event utilizing the second generation Grubbs catalyst. This process yields a polymer that can be precipitated with methanol or ether/hexane, leaving products in excellent yield and purity.
An improved method for the synthesis of sulfonylureas
Cervello,Sastre
, p. 221 - 222 (2007/10/02)
Treatment of isocyanates with sulfonamides in dimethylformamide in the presence of copper(I) chloride affords sulfonylureas in high yields under mild conditions.
Novel agents effective against solid tumors: The diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships
Howbert,Grossman,Crowell,Rieder,Harper,Kramer,Tao,Aikins,Poore,Rinzel,Grindey,Shaw,Todd
, p. 2393 - 2407 (2007/10/02)
A series of diarylsulfonylureas with exceptionally broad-spectrum activity against syngeneic rodent solid tumors in vivo is described. Their discovery resulted from a program dedicated to in vivo screening for novel oncolytics in solid tumor models, rather than traditional ascites leukemia models. The structures, oral efficacy, side-effect profile, and mechanism of action of these sulfonylureas appear to be distinct from previously known classes of oncolytics. An extensive series of analogues was prepared to probe structure-activity relationships (SAR), with particular focus on the substituent patterns of each aryl domain. Quantitative analysis of these substituent SARs, using the method of cluster significance analysis, showed the lipophilicity of the substituents to be the dominant determinant of activity. One compound from the series, LY186641 (104, sulofenur), has progressed to Phase I clinical trials as an antitumor drug.
