98-10-2

Usage

Uses

Used in Biospecific Adsorption:
Benzenesulfonamide is used as a component in self-assembled monolayers of alkanethiolates on gold, which facilitates the biospecific adsorption of carbonic anhydrase. This application aids in the development of a model system for studying lateral steric effects.
Used in Pharmaceutical Modifications:
Benzenesulfonamide is utilized in the modification of pharmaceutical compounds, such as ciprofloxacin, where its presence at the c-7 position alters the primary target in Streptococcus pneumoniae from topoisomerase IV to gyrase.
Used in the Development of COX-2 Inhibitors:
Polar substitutions in the benzenesulfonamide ring of celecoxib have been found to produce a potent 1,5-diarylpyrazole class of COX-2 inhibitors, which are important in the development of anti-inflammatory drugs.
Used in Environmental Analysis:
Benzenesulfonamide is employed in the development of analytical methods for the simultaneous determination of benzotriazole, benzothiazole, and benzenesulfonamide contaminants in environmental waters, contributing to the monitoring and control of water pollution.

Preparation

Benzenesulfonamide is obtained by amination of benzenesulfonyl chloride.

Synthesis Reference(s)

Tetrahedron Letters, 35, p. 7201, 1994 DOI: 10.1016/0040-4039(94)85360-6Synthesis, p. 1031, 1986 DOI: 10.1055/s-1986-31862

Biological Activity

benzenesulfonamide, the amide of benzenesulfonic acid, has been used to produce various derivatives, especially those used as intermediates in the synthesis of photochemicals, dyes, disinfectants, as well as pharmaceuticals.

Biochem/physiol Actions

Benzenesulfonamide is an inhibitor of human carbonic anhydrase B. Benzenesulfonamide derivatives are effective in the treatment of proliferative diseases such as cancer. It is used in the synthesis of dyes, photochemicals and disinfectants.

Safety Profile

Moderately toxic by ingestion andintraperitoneal routes. When heated to decomposition itemits very toxic fumes of SOx and NOx.

in vitro

in a previous study, a series of n-aryl-β-alanine- and diazo-derivatives of benzenesulfonamide were designed, synthesized, and their binding affinities to carbonic anhydrases (ca) i, ii, vi, vii, xii, and xiii was investigated by the use of isothermal titration calorimetry and fluorescent thermal shift assay. the results indicated that 4-substituted diazobenzenesulfonamides were found to be most potent ca binders among the synthesized derivatives. in addition, the majority of the n-aryl-β-alanine derivatives had better affinity for ca ii while diazobenzenesulfonamides showed nanomolar affinities towards ca i isozyme. moreover, the x-ray crystallographic data showed the binding modes of both derivative groups [1].

in vivo

in the rat cpe model, the most potnet benzenesulfonamide indole derivative at 10 mg/kg in the mc/tw formulation displayed oral efficacy. moreover, Benzenesulfonamide, when administered in another preferred, minimal formulation in the same in vivo model, demonstrated superior oral efficacy to the lead phenylmethane sulfonamide way-196025 orally administered in a lipid-based formulation. in addition, this benzenesulfonamide indole derivative was also orally efficacious at 1 mg/kg by attenuating both lar and the associated ahr to aerosolized carbachol in naturally sensitized sheep, which had been challenged through the airways with a. suum antigen [2].

references

[1] rutkauskas k et al. 4-amino-substituted benzenesulfonamides as inhibitors of human carbonic anhydrases. molecules. 2014 oct 28;19(11):17356-80. [2] lee kl et al. benzenesulfonamide indole inhibitors of cytosolic phospholipase a2α: optimization of in vitro potency and rat pharmacokinetics for oral efficacy. bioorganic and medicinal chemistry. 2008 16(3), 1345-1358.

InChI:InChI=1/C6H7NO2S/c7-10(8,9)6-4-2-1-3-5-6/h1-5H,(H2,7,8,9)

Upstream product

• 110-86-1 pyridine 
• 857485-27-9 [2-(1-acetyl-2-oxo-propylsulfanyl)-benzoyl]-benzenesulfonyl-amine 
• 177786-68-4 2,2'-disulfanediyl-di-benzoic acid bis-benzenesulfonylamide 
• 123-54-6 acetylacetone 
• 120-72-9 indole 
• 53497-62-4 N-piperidinomethyl-benzenesulfonamide 
• 938-10-3 phenylsulfonyl azide 
• 938-05-6 dibromamine-B 
• 60-29-7 diethyl ether 
• 64-17-5 ethanol 
• 16066-31-2 benzenesulfinamide 
• 368-43-4 phenylsulfonyl fluoride 
• 56-23-5 tetrachloromethane 
• 55-21-0 benzamide 

Downstream Products

• 17927-88-7 2-(phenylsulfonyl)benzo[d]isothiazol-3(2H)-one 
• 59724-42-4 N-(2-hydroxyethyl)benzenesulfonamide 
• 13127-79-2 N-benzenesulfonyl-bis(2-hydroxyethyl)amine 
• 53497-62-4 N-piperidinomethyl-benzenesulfonamide 
• 4392-61-4 N-morpholin-4-ylmethyl-benzenesulfonamide 
• 4936-04-3 1,4-bis-(benzenesulfonylamino-methyl)-piperazine 
• 6326-01-8 N-xanthen-9-yl-benzenesulfonamide 
• 14744-31-1 (E)-N-(furan-2-ylmethylene)benzenesulfonamide 
• 4083-65-2 N,N'-bis-benzenesulfonyl-oxalamide 
• 90668-97-6 benzenesulfonyl-oxalamic acid methyl ester 
• 17436-26-9 benzenesulfonyl-imidophosphoric acid triphenyl ester 
• 78542-90-2 N,N'-bis-benzenesulfonyl-succinamide 
• 83102-63-0 benzenesulfonyl-bis-(4-nitro-benzenesulfenyl)-amine 
• 80480-21-3 N-hydroxymethyl-benzenesulfonamide 

Relevant academic research and scientific papers

MECHANISTIC INVESTIGATIONS WITH POSITIVE HALOGENS: KINETICS OF OXIDATION OF THIOSEMICARBAZIDE BY CHLORAMINE-B, BROMAMINE-B AND DICHLORAMINE-B IN ACID MEDIUM

Kinetics of oxidation of thiosemicarbazide (TSC) by chloramine-B (CAB), and bromamine-B (BAB) in aqueous perchloric acid medium and by dichloramine-B (DCB) in 1:1 (v/v) water-methanol medium has been studied.The rate followed first order kinetics in and inverse fractional order in with all the oxidants.But it was fractional order in with CAB and independent of with BAB and DCB.Addition of benzenesulphonamide, the reduced product of the oxidants had no effect on the rate with CAB and BAB but it slightly increased the rate with DCB.Therate decreased with increase in ionis strength of the medium in all cases.Decrease of dielectric constant of the reaction medium by adding methanol had no effect on the rate with CAB and BAB but increased the rate with DCB.The mechanisms proposed and the derived rate laws are in conformity eith the observed results.The coefficients of the rate limiting steps have been calculated.Kinetics observed with HOCl and HOBr support the proposed mechanisms.

Osmium(VIII)-catalyzed kinetics and mechanism of indigo carmine oxidation by chloramine-B in basic medium

Indigo carmine (IC) or sodium indigotin disulfonate is a natural dye that finds applications in clinical diagnosis, chemistry and biology. The osmium(VIII)-catalyzed oxidation of IC by chloramine-B (CAB) in alkaline solutions has been spectrophotometrically monitored at the indigo carmine λmax of 610 nm at 298 K. The reaction stoichiometry has been found to be 1:4 (mol:mol), resulting in the formation of major products that are the sodium salt of sulfonated anthranilic acid (SAA) and benzenesulfonamide (BSA). The reaction shows a first-order dependence of the rate on [IC], a fractional-order dependence each on [Os(VIII)] and [OH-], and a zero-order dependence each on [CAB], [BSA], and [SAA]. The variation of the ionic strength of the reaction medium has a negligible effect on the rate. Based on the effect of temperature in the range 288-313 K, activation parameters are evaluated from Arrhenius and Eyring plots. A mechanism consistent with the observed kinetic and activation data has been proposed and a rate law has been derived. Copyright Taylor & Francis Group, LLC.

Synthesis and X-Ray Structure of Bistetraphenylphosphonium Tris(phenylsulphonylimino)sulphite

An aza-analogue of sulphite, the structure of which was determined by X-ray diffraction, is prepared from sodium amide and a sulphur di-imide in liquid ammonia.

Chloraminometric and bromaminometric oxidation of sulfanilic acid in alkaline medium: A comparative kinetic and mechanistic study

The kinetics of oxidation of sulfanilic acid (SAA) by chloramine-B (CAB) and bromamine-B (BAB) has been investigated in alkaline medium at 35 ± 0.1°C. The oxidation reaction follows identical kinetics in the case of both the oxidants with first-order dependence on each [oxidant]o and [SAA]o and an inverse first-order dependence on [OH-]. The variation of ionic strength, dielectric constant of the medium, addition of the reaction product (benzene-sulfonamide), and halide ions showed no significant influence on the reaction rate. Proton inventory studies made in H2O-D2O mixtures for CAB and BAB have been utilized to calculate the isotopic fractionation factor. The reaction has been studied at different temperatures, and activation parameters for the composite reaction have been computed from the Arrhenius plots. N-Hydroxylaminobenzene-4-sulfonic acid was identified as the oxidation product of SAA from IR and GC-MS analysis. A mechanism consistent with the kinetic results is proposed in which PhSO 2NHX (X = Cl or Br) interact with the substrate in the rate-limiting step. A suitable rate law is derived. The rate of oxidation of sulfanilic acid is about fourfold faster in BAB compared to CAB. The oxidation of SAA brought about by CAT and BAT was also investigated under identical experimental conditions, and the overall rate of oxidation of SAA increases in the order: BAB > BAT > CAB > CAT This may be attributed to the difference in electrophilicities of Cl+ and Br+ ions and also the van der Waal's radii of chlorine and bromine.

SELECTIVE NON-CYCLIC NUCLEOTIDE ACTIVATORS FOR THE CAMP SENSOR EPAC1

The invention relates generally to novel EPAC1 activators, such as Formula (I) and (II) and the preparation thereof as well as the use of EPAC1 activators disclosed herein as to selectively activate EPAC1 in cells.

Synthesis, biological evaluation, and docking studies of novel pyrrolo[2,3-b]pyridine derivatives as both ectonucleotide pyrophosphatase/phosphodiesterase inhibitors and antiproliferative agents

Ecto-nucleotide pyrophosphatases/phosphodiesterases (NPPs) together with nucleoside triphosphate diphosphohydrolases (NTPDases) and alkaline phosphatases (APs) are nucleotidases located at the surface of the cells. NPP1 and NPP3 are important members of NPP family that are known as druggable targets for a number of disorders such as impaired calcification, type 2 diabetes, and cancer. Sulfonylurea derivatives have been reported as antidiabetic and anticancer agents, therefore, we synthesized and investigated series of sulfonylurea derivatives 1a-m possessing pyrrolo[2,3-b]pyridine core as inhibitors of NPP1 and NPP3 isozymes that are over-expressed in cancer and diabetes. The enzymatic evaluation highlighted compound 1a as selective NPP1 inhibitor, however, 1c was observed as the most potent inhibitor of NPP1 with an IC50 value of 0.80 ± 0.04 μM. Compound 1l was found to be the most potent and moderately selective inhibitor of NPP3 (IC50 = 0.55 ± 0.01 μM). Furthermore, in vitro cytotoxicity assays of compounds 1a-m against MCF-7 and HT-29 cancer cell lines exhibited compound 1c (IC50 = 4.70 ± 0.67 μM), and 1h (IC50 = 1.58 ± 0.20 μM) as the most cytotoxic compounds against MCF-7 and HT-29 cancer cell lines, respectively. Both of the investigated compounds showed high degree of selectivity towards cancer cells than normal cells (WI-38). Molecular docking studies of selective and potent enzyme inhibitors revealed promising mode of interactions with important binding sites residues of both isozymes i.e., Thr256, His380, Lys255, Asn277 residues of NPP1 and His329, Thr205, and Leu239 residues of NPP3. In addition, the most potent antiproliferative agent, compound 1h, doesn't produce hypoglycemia as a side effect when injected to mice. This is an additional merit of the promising compound 1h.

Synthesis of magnetic chitosan supported metformin-Cu(II) complex as a recyclable catalyst for N-arylation of primary sulfonamides

The application of chitosan, which has received much attention as a natural polymer and effective support, has many advantages such as biodegradability and biocompatibility. In this study, the immobilization of a copper complex on the magnetic chitosan bearing metformin ligand has been developed through immobilizing structurally defined metformin with long tail of (3-chloropropyl)trimethoxysilane (TMOS). The synthesized Fe3O4-chitosan@metformin-Cu(II) complex (Fe3O4-CS@Met-Cu(II)) was used as an effective, reusable and magnetic catalyst in the N-arylation of different derivatives of primary sulfonamides with arylboronic acids in ethanol. The primary sulfonamides were prepared from the reaction of sulfonyl chlorides with sodium cyanate in water under ultrasonic irradiation. Utilizing a wide variety of substrates in EtOH as a green solvent, high yields of the primary and secondary sulfonamides, easy work-up along with the excellent recovery and reusability of the catalyst, make this process a simple, economic and environmentally benign method. The synthesized Fe3O4-CS@Met-Cu(II) was characterized using various techniques such as XRD (X-ray diffraction), EDS (energy-dispersive X-ray spectroscopy), elemental mapping, TEM (transmission electron microscopy), FESEM (field emission scanning electron microscopy), VSM (vibrating sample magnetometer), ICP-MS (inductively coupled plasma mass spectroscopy), TGA (thermogravimetric analysis) and FT-IR (Fourier-transform infrared spectroscopy) analyses. The catalyst can be recycled and reused 5 times with no considerable loss of catalytic activity.

Development of succinimide-based inhibitors for the mitochondrial rhomboid protease PARL

While the biochemistry of rhomboid proteases has been extensively studied since their discovery two decades ago, efforts to define the physiological roles of these enzymes are ongoing and would benefit from chemical probes that can be used to manipulate the functions of these proteins in their native settings. Here, we describe the use of activity-based protein profiling (ABPP) technology to conduct a targeted screen for small-molecule inhibitors of the mitochondrial rhomboid protease PARL, which plays a critical role in regulating mitophagy and cell death. We synthesized a series of succinimide-containing sulfonyl esters and sulfonamides and discovered that these compounds serve as inhibitors of PARL with the most potent sulfonamides having submicromolar affinity for the enzyme. A counterscreen against the bacterial rhomboid protease GlpG demonstrates that several of these compounds display selectivity for PARL over GlpG by as much as two orders of magnitude. Both the sulfonyl ester and sulfonamide scaffolds exhibit reversible binding and are able to engage PARL in mammalian cells. Collectively, our findings provide encouraging precedent for the development of PARL-selective inhibitors and establish N-[(arylsulfonyl)oxy]succinimides and N-arylsulfonylsuccinimides as new molecular scaffolds for inhibiting members of the rhomboid protease family.

Unlocking Amides through Selective C–N Bond Cleavage: Allyl Bromide-Mediated Divergent Synthesis of Nitrogen-Containing Functional Groups

We report a new set of reactions based on the unlocking of amides through simple treatment with allyl bromide, creating a common platform for accessing a diverse range of nitrogen-containing functional groups such as primary amides, sulfonamides, primary amines, N-acyl compounds (esters, thioesters, amides), and N-sulfonyl esters. The method has potential industrial applicability, as demonstrated through gram-scale syntheses in batch and in a continuous flow system.

Synthesis of new Copper Catalyst with Pyrazole Based Tridentate Ligand and Study of Its Activity for Azide Alkyne Coupling

Synthesis of new copper catalyst with pyrazole based tridentate ligand and study of its activity for azide alkyne coupling were investigated by researchers. To a solution of acetyl acetone (2.002 g, 20 mmol), 2- nitrophenylhydrazine in ethanol was added five drops of con. HCl and heated at 50° for 1 hour. After confirming the formation of 3, 5-dimethyl-1-(2-nitrophenyl)- 1H-pyrazole by TLC, ice cooled water was added in to the reaction mixture. The precipitate was filtered, washed with water and then hexane. The product formed as yellow precipitate, that precipitate had been filtered by normal filter paper. The product was recrystallized in ethanol. For synthesis, was suspended in 6 mL of deionized and stirred for 4 h until a clear solution was obtained in 50 ml round bottom flask Cu(OAc) 2. The reaction mixture was diluted with water, filtered, washed sequentially with water, methanol and n-hexane. Then dark greenish blue color crystal were formed and used for the reactions. The solid was crystallized in CH2Cl2 to get crystal whose structure was confirmed by single crystal XRD.