13947-21-2

Usage

InChI:InChI=1/C8H6ClNO3S/c9-5-10-8(11)6-3-1-2-4-7(6)14(10,12)13/h1-4H,5H2

Upstream product

• 13947-20-1 N-(hydroxymethyl)saccharin 
• 870-72-4 sodium formaldehyde bisulfite 
• 81-07-2 saccharin 
• 50-00-0 formaldehyd 

Downstream Products

• 106841-62-7 2-(benzylmercapto-methyl)-1,1-dioxo-1λ⁶-benz[d]isothiazol-3-one 
• 40431-34-3 2-(hydroxymethyl)-N-methylbenzenesulfonamide 
• 54553-16-1 2-(diphenylphosphanyl-methyl)-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[d]isothiazol-3-one 
• 21081-64-1 2-(3-nitrobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide 
• 3416-59-9 N-benzylsaccharin 
• 109538-88-7 2-((4-nitrophenoxy)methyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide 
• 150810-11-0 N-<(phenylthioacetoxy)methyl>saccharin 
• 134697-04-4 N-[4-(1,1,3-Trioxo-1,3-dihydro-1λ⁶-benzo[d]isothiazol-2-ylmethoxy)-phenyl]-acetamide 
• 150423-20-4 2-((4-chlorophenoxy)methyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide 
• 134697-02-2 2-((4-methoxyphenoxy)methyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide 
• 150423-21-5 2-(4-Acetyl-phenoxymethyl)-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[d]isothiazol-3-one 
• 134697-03-3 1,1-Dioxo-2-phenoxymethyl-1,2-dihydro-1λ⁶-benzo[d]isothiazol-3-one 
• 157231-19-1 17β-estradiol 3'-(saccharinylmethyl) ether 
• 936256-39-2 methyl [2-(methoxycarbonyl)phenylsulfonamido]methylsulfonate 

Relevant academic research and scientific papers

Retro-ene reactions. III. Alkylation of 4,5-dichloro-1-hydroxymethylpyridazin-6-ones: Synthesis of 4,5-dichloro-1-(ω-phthalimido and saccharin-2′-ylalkyl)pyridazin-6-ones

4,5-Dichloro-1-(ω-phthalimido and saccharinyl-2′-ylalkyl)pyridazin-6-ones were synthesized from 4,5-dichloro-1-hydroxymethylpyridazin-6-one and the corresponding N-(ω-haloalkyl)phthalimides and saccharins via a fragmentation of retro-ene type.

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.

NMR study of the tautomeric behavior of N -(α-Aminoalkyl)tetrazoles

N-(α-Aminoalkyl)tetrazoles exist in solution as equilibrium mixtures of N1 and N2 tautomers. The position of equilibrium depends significantly on the polarity of the solvent and the substituents in the tetrazole ring. Interconversion between individual tautomers is shown to proceed via tight ion-pair intermediates in which intramolecular recombination is faster than the intermolecular crossover since the latter probably requires solvent separation of ion-pair intermediates.

Facile one-pot synthesis of 4-hydroxy-2-methyl-(2H)-1,2-benzothiazine-3- sulfonic acid 1,1-dioxide

We report a convenient synthesis of 4-hydroxy-2-methyl-(2H)-1,2- benzothiazine-3-sulfonic acid-1,1-dioxide (6a) prepared in a novel one-pot reaction. The synthesis involves two transformations starting from 2-methyl-2H-1,2-benzothiazin-4-(3H)-one 1,1-dioxide (7) with an overall yield better than that from the stepwise process, as well as the alternate procedure starting from saccharin (1). One-pot synthesis of an important intermediate, saccharin-N-methane sulfonic acid (4), is also described. Copyright Taylor & Francis Group, LLC.

Synthesis and photophysical properties of N-styrylazinones

(Chemical Equation Presented) N-Styrylazinones and 1-styrylbenzotriazine were synthesized, and their photophysical properties were investigated. (Z)- and/or (E)-N-Styrylazinones (or azine) 4 were prepared from the corresponding heterocycles 1 and benzaldehyde (3) by four methods. The absorption maxima of (Z)- and/or (E)-4a - 4j were measured in four solvents. Their absorption maxima showed a moderate dependence upon solvents. The absorption maxima of (Z)-isomers were blue-shifted as compared the corresponding (E)-isomers. Emission maxima, fluorescence band half-widths, 0,0 transition energies, Stokes shifts, and quantum yields of (Z)- and/or (E)-4a, 4b, 4d, 4e and 4j were measured in organic solvents. The fluorescence spectra show moderate solvatochroism. The fluorescence properties of N-styrylheterocycles vary with every heterocycles.

Synthesis, antimycobacterial and antitumor activities of new (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl N,N-disubstituted dithiocarbamate/O-alkyldithiocarbonate derivatives

Reaction of 2-chloromethylsaccharin with substituted potassium dithiocarbamates and substituted potassium dithiocarbonates furnished (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl N,N-disubstituted dithiocarbamates (4-15) and (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl O-alkyldithiocarbonates (16-20). The new derivatives were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Compounds 4-13, 15, and 16-20 described herein showed moderate to good inhibitory activity. In particular, seven analogs 4, 5, 6, 13, and 7, 8, and 12 exhibited excellent MIC values of 1.56 and 0.78 μg/mL, respectively. Compounds 4, 5, 10, 12, 13, and 16 were selected and screened for antitumor activity. Among the tested compounds, 4 and 5 were found to be cytotoxic, especially against leukemia cell lines CCRF-CEM, HL-60(TB), RPMI-8226, and SR with log10 GI50 values lower than -6.69, and against non-small cell lung cancer NCI-H522 cell line with log10 GI50 values lower than -6.31. Compound 10 was cytotoxic against leukemia cell line HL-60(TB), whereas 16 displayed favorable cytotoxicity against ovarian cancer cell line OVCAR-3 with log10 GI50 values of -6.31 and -7.45, respectively.

A one-step protocol for the N-chloromethylation of heterocyclic imides

A convenient single step methodology for the N-chloromethylation of heterocyclic imides using a mixture of formaldehyde sodium bisulfite adduct and thionyl chloride is described.

A prodrug approach to increasing the oral potency of a phenolic drug. 1. Synthesis, characterization, and stability of an O-(imidomethyl) derivative of 17β-estradiol

An O-(saccharinylmethyl) prodrug was synthesized to improve the poor oral potency of the phenolic drug 17β-estradiol. This O-(imidomethyl) type of prodrug was designed to undergo chemical hydrolysis and to be a poor substrate for enzymatic hydrolysis. At 37 °C, it was found to exhibit half- lives of about 13 min in 50% methanol:pH 7.0 (v/v) phosphate buffer, about 3 min in rat plasma, about 15 min in human plasma, and about 50 min in 20% rat liver homogenate. Introduction of the enzyme poison tetraethyl pyrophosphate or the protein denaturant sodium fluoride into rat plasma had no significant effect on the half-life. Thus, the observed increased rate of hydrolysis in biological media is not due to enzymatic catalysis but to a nonspecific solventlike effect. The fact that the rate of hydrolysis in the methanol:buffer exhibited a first-order dependence on the hydroxide ion concentration and that the rate of hydrolysis increased with increasing methanol concentrations up to 70% supported an S(N)2 mechanism of hydrolysis for the prodrug. These results suggest that an O-(imidomethyl) type prodrug is insensitive to enzymatic catalysis of hydrolysis yet may hydrolyze quickly enough to release 17β-estradiol faster than 17β-estradiol is conjugated and excreted.

Mechanism of Hydrolysis of O-Imidomethyl Derivatives of Phenols

Three series of O-imidomethyl derivatives of para-substituted phenolic compounds were synthesized and their rates of hydrolysis were studied.Saccharin, phthalimide, and succinimide served as the imide portions of the derivatives.Their rates of hydrolysis were found to be first order with respect to hydroxide from pH 7.0 to 10 or 11 and dependent on the acidity (leaving group potential) of both the imide and the phenol portions.The more acidic the imide or the phenol, the faster the rate of hydrolysis.However, the rates of hydrolysis were more sensitive to the acidity of the phenol.Trapping experiments with cyanide also suggested that the phenol anion was functioning as the leaving group in what is apparently an SN2 reaction.An amide derivative was found to hydrolyze more slowly than predicted from the analogous series and the pKa of the amide.This result is apparently due partially stereoelectronic constraints in the imide series that cause the CH2-O bond to be oriented more nearly perpendicular to the plane of the C(=O)N group and hence more accessible to nucleophilic attack.

Efficient Inhibition of Human Leukocyte Elastase and Cathepsin G by Saccharin Derivatives

A series of saccharin derivatives I has been synthesized and evaluated for their inhibitory activity toward human leukocyte elastase and cathepsin G.Most of the compounds were found to be efficient and time-dependent inhibitors of elastase.Inactivated elastase was found to regain its activity almost fully after 24 h (80-90 percent activity) and the half-lives of reactivation ranged between 12-15 h.Addition of hydroxylamine to fully-inactivated enzyme led to rapid and complete recovery of enzymatic activity.A tentative mechanism of action is proposed on the basis of biochemical and model studies.