- Benzenesulfonamide bearing imidazothiadiazole and thiazolotriazole scaffolds as potent tumor associated human carbonic anhydrase IX and XII inhibitors
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Two series of 20 novel heterocyclic compounds, imidazothiadiazoles (3a-3j) and thiazolotriazoles (4a-4j) bearing benzenesulfonamide moiety were synthesized in order to investigate the inhibition potential of both scaffolds against four selected human carbonic anhydrase isoforms (hCA I, II, IX & XII). Against human isoform hCA I, compounds 3j, 4a-4c, and 4j showed better inhibition potential (Ki??100?nM) than the standard drug acetazolamide (AZA). Against hCA II, all the compounds showed moderate inhibition with the exception of 3a which showed nearly two fold better profile compared to AZA. Against hCA IX, all the compounds showed moderate inhibitory potential than AZA, whereas against hCA XII, compounds 3a-3c showed better inhibitory potential compared to AZA.
- Kumar, Rajiv,Bua, Silvia,Ram, Sita,Del Prete, Sonia,Capasso, Clemente,Supuran, Claudiu T.,Sharma, Pawan K.
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- Tail approach synthesis of novel benzenesulfonamides incorporating 1,3,4-oxadiazole hybrids as potent inhibitor of carbonic anhydrase I, II, IX, and XII isoenzymes
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Two new series of 1,3,4-oxadiazole benzenesulfonamide hybrids 3 and 4, having twenty novel compounds, have been designed and synthesized in order to assess their inhibition potential as CAIs against hCA I, II, IX, and XII. ‘Tail approach’ strategy has been used to design the aromatic sulfonamide scaffolds with carbonyl and amide linker. Excellent inhibitory activity against hCA I has been exhibited by compounds 3g and 4j, 3.5 magnitude of order better than reference drug AAZ (KI = 250 nM). Moreover, compound 4j (KI = 7.9 nM) effectively inhibited glaucoma-associated hCA II isoform as well as tumor-associated hCA IX isoform with KI = 16.3 nM. Further hCA XII was weakly inhibited by all the compounds with KI values ranging from 0.23 μM to 3.62 μM. Interestingly structure-activity relationship (SAR) study indicates that N-(3-nitrophenyl)-2-((5-(4-sulfamoylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetamide (4j) is a potent compound to be investigated further for antiglaucoma and antitumor activity. The chemistry of the nature of different substitutions on the 1,3,4-oxadiazole bearing benzenesulfonamide substituted aromatic ring for potency and selectivity over one hCA isoform versus others is deliberated in the present study. In this context, the 1,3,4-oxadiazole motif can be a valuable tool worth developing for the procurement of novel and potent selective CAIs potentially useful for the management of a variety of diseases as chemotherapeutic agents.
- Angeli, Andrea,Kumar, Rajiv,Sharma, Pawan K.,Sharma, Vikas,Supuran, Claudiu T.
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- Palladium-Catalyzed ortho-Benzoylation of Sulfonamides through C?H Activation: Expedient Synthesis of Cyclic N-Sulfonyl Ketimines
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The ortho-carbonylation of sulfonylarenes by non-hazardous aryl aldehydes as a carbonyl precursor was reported. In this method, the sulfonamide group serves as a directing group for C?H activation in the presence of a Pd catalyst under ligand-free conditions. The scope of this strategy has been extended to the one-pot two-step synthesis of cyclic N-sulfonyl ketimines under mild reaction conditions. Our approach could be considered as an alternative by circumventing the use of highly reactive organolithium or Grignard reagents to access a wide range of biologically potent cyclic N-sulfonyl ketimines. (Figure presented.).
- Ojha, Subhadra,Panda, Niranjan
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p. 561 - 571
(2019/12/24)
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- Sulfonamide compound and synthesis method and application thereof
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The invention discloses a synthesis method of a sulfonamide compound represented in a formula (2). According to the method, diazonium salt is used as a reaction raw material, and under the action of an inorganic nitrogen reagent, an inorganic sulfur dioxide reagent, an additive and a phosphine reagent, the diazonium salt is reacted in a solvent at 60-100 DEG C to obtain various sulfonamide compounds. According to the method inorganic salt is used as a nitrogen atom source and a sulfur dioxide source under a metal-free catalytic condition to construct the sulfonamide compound through one step,thereby avoiding the conventional multi-step synthesis of sulfonamide by condensing unstable acid chloride and amine; and the developed sulfonamide synthesis method can be further applied to the synthesis of the arthritis drug celecoxib and the psychotropic drug sulpiride.
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Paragraph 0138-0141
(2019/04/02)
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- Metal-free construction of primary sulfonamides through three diverse salts
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In this report, the first metal-free construction of primary sulfonamides through a direct three-component reaction of sodium metabisulfite, sodium azide and aryldiazonium has been established. Readily available inorganic Na2S2O5 and NaN3 were applied as the sulfur dioxide surrogate and nitrogen source respectively. The widely used sulfonamide drugs Celecoxib and Sulpiride, which possess multiple heteroatoms and active hydrogen containing functional groups, are efficiently installed with -SO2NH2 groups at a late stage. Control experiments and kinetic studies demonstrated that aryl radicals, sulfonyl radicals and conjugated phosphine imine radicals are involved in this transformation.
- Wang, Ming,Fan, Qiaoling,Jiang, Xuefeng
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supporting information
p. 5469 - 5473
(2019/01/03)
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- Drug synthesis intermediate carzenide synthesis method
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The invention discloses a drug synthesis intermediate carzenide synthesis method, which comprises: adding 2-methyl-4-hydroxy-3,6-dihydroxymethyl toluene and a 2,4-pentanedione solution into a reactioncontainer, controlling the stirring speed, increasing the temperature of the solution, adding gadolinium oxide in batches, washing multiple times with a sodium sulfate solution, washing multiple times with a 2-methyl-2,4-pentanediol solution, washing multiple times with a 3-methyl furan solution, adjusting the pH value with an oxalic acid solution, re-crystallizing in a 3-methyl-2-butanone solution, and dehydrating with a dehydrating agent to obtain the finished product carzenide.
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Paragraph 0014; 0018-0029
(2018/07/30)
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- Method for oxidatively synthesizing p-carboxybenzene sulfonamide through oxygen
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The invention discloses a method for oxidatively synthesizing p-carboxybenzene sulfonamide through oxygen, and belongs to a method for preparing p-carboxybenzene sulfonamide.The method comprises the steps that oxygen is taken as an oxidizing agent, the oxygen pressure only needs to be maintained at 1 atm, and an oxidizing reaction is conducted in acetic acid by taking oxygen as the oxidizing agent under the action of a nitroxide free radical type catalyst and a metal salt or metallic oxide cocatalyst; p-methylphenyl sulphonylamine is catalytically oxidized to prepare p-carboxybenzene sulfonamide.The method comprises the processes that 5 mL of acetic acid, 1 mmol of p-methylphenyl sulphonylamine, the catalyst and the cocatalyst are sequentially added in a round-bottom flask with a magnetic stirring device, oxygen is introduced, and the pressure is maintained at 1 atm; the dosage mole ratio of the catalyst is 3%-8% of that of p-methylphenyl sulphonylamine, the dosage mole ratio of the cocatalyst is 0.5%-6% of that of p-methylphenyl sulphonylamine, reacting is finished after stirring is performed for 2-12 hours at the temperature of 40 DEG C-120 DEG C, cooling is performed, reduced pressure distillation is performed to remove acetic acid, residues are sequentially washed with water and acetone, and drying is performed to obtain p-carboxybenzene sulfonamide.The method has the advantages that the conditions are mild, and the yield is high.
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Paragraph 0048
(2016/12/01)
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- Preparation method for p-carboxybenzene sulfonamide
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The invention relates to the field of organic synthesis, and discloses a preparation method for p-carboxybenzene sulfonamide. The method comprises the following step: making a compound shown as a formula (1), alkali metal halate and protonic acid contact one another in water in the presence of alkali metal halide salt, wherein the alkali metal halate is selected from one or more of LiBrO3, KBrO3 and NaBrO3; the alkali metal halide salt is selected from one or more of LiBr, KBr and NaBr. The method has the advantages of simple steps and environmental friendliness, and pollution caused by use of a heavy metal oxidant is avoided.
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Paragraph 0044; 0045; 0046
(2016/10/08)
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- Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII
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Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII.
- Sitaram,Celik, Gulsah,Khloya, Poonam,Vullo, Daniela,Supuran, Claudiu T.,Sharma, Pawan K.
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p. 1873 - 1882
(2014/03/21)
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- Sulfonyl-containing 2,3-diarylindole compounds, methods for making same, and methods of use thereof
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The present invention relates to sulfonyl-containing 2,3-diarylindole, especially to new compounds of general Formula, to a preparation method for their preparation, to pharmaceutical compositions containing said compound, and to the medical use thereof in the treatment of diseases relating to the inhibition of cyclooxygenase-2 (COX-2).
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Page/Page column 8; 14
(2010/02/06)
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- SUBSTITUTED (AMINOIMINOMETHYL OR AMINOMETHYL) BENZOHETEROARYL COMPOUNDS
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This invention is directed to an (aminoiminomethyl or aminomethyl) benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.
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- Cobalt(II) chloride-catalyzed chemoselective sodium borohydride reduction of azides in water
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Reduction of azides to amines and amides was carried out with NaBH4/CoCl2·6H2O in sole water at 25 °C under catalytic heterogeneous conditions. A broad spectrum of azides was reduced in a short time, chemoselectively in high yield and purity.
- Fringuelli, Francesco,Pizzo, Ferdinando,Vaccaro, Luigi
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p. 646 - 650
(2007/10/03)
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- Substituted pyrrolyl compounds for the treatment of inflammation
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A class of pyrrolyl derivatives is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I STR1 wherein R1, R2, R3 and R4 are as described in the specification.
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- Synthesis and Evaluation of Multisubstrate Inhibitors of an Oncogene-Encoded Tyrosine-Specific Protein Kinase. 1
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The synthesis and testing of potental multisubstrate inhibitors of tyrosine-specific protein kinases are described.One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics.The resulting multisubstrate inhibitors were tested for their ability to inhibit the transfer of phosphate from ATP to a protein acceptor by p60v-abl, the tyrosine kinase encoded by the transforming gene (v-abl) of the Abelson murine leukemia virus (A-MuLV).Although the series of inhibitors displayed moderately potent activity (IC50 values as low as 19 μM), the absence of large effects produced by modification of the tyrosine mimic suggests that they do not behave as multisubstrate inhibitors but bind primarily through the adenosine moiety common to all the inhibitors.This interpretation is strengthened by the findings that the inhibitors lack specificity, inhibiting a serine kinase at compatible concentrations.
- Kruse, Carolyn H.,Holden, Kenneth G.,Pritchard, M. Lynn,Feild, John A.,Rieman, David J.,et al.
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p. 1762 - 1767
(2007/10/02)
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