Cyclic Sulfonamide Research Articles

A novel regiospecific cascade synthesis of sulfonamide derivatives from N-(2-polychloroethyl)sulfonamides via chloroaziridine intermediates in the presence of mercaptoethanol

N-(1-Aryl-2-polychloroethyl)arenesulfonamides obtained on the basis of N,N-dichlorosulfoamides and polychloroethenes or phenylacetylene undergo a reaction cascade in the presence of mercaptoethanol. The reaction cascade opens a new route to the series of cyclic or open-chain sulfonamide derivatives. The process includes cyclization to aziridine intermediates, their further recyclization, and isomerization to imidoylchlorides or chloroimines, followed by substitution or reduction under the action of mercaptoethanol or hydrolysis. The final sulfonamide structures depend on the starting N-(polychloroethyl)sulfonamides. N-(2,2-Dichloroethyl)sulfonamides were transformed into sulfonamide-containing 1,4-oxathians while N-(2,2,2-trichloroethyl)sulfonamides were converted to N-(2-arylacetyl)arenesulfonamides. N-(2-Phenyl-2,2-dichloroethyl)sulfonamides form enamide derivatives that were transformed into aromatic ketones.

ChemInform Abstract: Novel 1β‐Methylcarbapenems Having Cyclic Sulfonamide Moities: Synthesis and Evaluation of in vitro Biological Activity. Part 2.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Discovery of cyclicsulfonamide derivatives as 11β-hydroxysteroid dehydrogenase 1 inhibitors

A new series of cyclic sulfonamide derivatives was synthesized and evaluated for their ability to inhibit 11β-HSD1. Cyclic sulfonamides with phenylacetyl substituents at the 2-position showed nanomolar inhibitory activities. Among them, compound 4e exhibited a good in vitro inhibitory activity and selectivity toward human 11β-HSD2.

Novel lβ‐Methylcarbapenems Having Cyclic Sulfonamide Moieties: Synthesis and Evaluation of in‐vitro Biological Activity – Part II

The synthesis of a new series of 1beta-methylcarbapenems having cyclic sulfonamide moieties is described. Their in-vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of a substituent on the pyrrolidine ring was investigated. One particular compound IIIe having a [1,2,5]thiadiazolidin 1,1-dioxide moiety showed the most potent antibacterial activity.

ChemInform Abstract: Synthesis and Antibacterial Activities of Novel Oxazolidinones Having Cyclic Sulfonamide Moieties.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Two enantiomerically pure cyclic arenesulfonamide hydrochloride salts

The crystal structures of N-[(1R)-1-(1-naphthyl)ethyl]-3,4-dihydro-2H-1,2-benzothiazin-4-aminium 1,1-dioxide chloride, C(20)H(21)N(2)O(2)S(+).Cl(-), (I), a six-membered cyclic sulfonamide, and (1R)-N-[(5,5-dioxo-6,7-dihydrodibenzo[d,f][1,2]thiazepin-7-yl)methyl]-1-(1-naphthyl)ethanaminium chloride, C(26)H(25)N(2)O(2)S(+).Cl(-), (II), a seven-membered cyclic sulfonamide, both representative of a novel family of agonists of the extracellular calcium sensing receptor (CaSR) of possible clinical importance, are reported. The known chirality of the naphthylethylamine precursor has enabled assignment of the absolute configuration of both compounds, which is crucial for the receptor recognition. The crystal structures, though different, reveal for these agonists a notable absence of intramolecular pi-pi stacking between their respective aromatic groups. This suggests a common structural feature that allows CaSR agonists to be distinguished from antagonists, since in the latter, such interactions have been shown to be important. The connectivities between molecules in the crystal structures are also different, but both involve hydrogen bonding mediated by chloride ions as a common dominant feature.

Synthesis and antibacterial activities of novel oxazolidinones having cyclic sulfonamide moieties

The synthesis of a new series of oxazolidinones having cyclic sulfonamide moieties is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the oxazolidinone ring was investigated. A particular compound 15g having [1,2,5]thiadiazolidin-1,1-dioxide moiety showed the most potent antibacterial activity.

Molecular Structure and Dynamic Properties of a Sulfonamide Derivative of Glutathione That Is Produced Under Conditions of Oxidative Stress by Hypochlorous Acid

Reduced glutathione (GSH) is a cornerstone of the antioxidant stratagem for eukaryotes and some prokaryotes. Hypochlorous acid (HOCl), which is produced by neutrophilic myeloperoxidase, reacts rapidly with excess GSH to yield mainly oxidized glutathione (GSSG). GSSG can be further oxidized to give first N-chloro derivatives and, later, higher oxidation states at the S centers. Under certain conditions, another major species that is observed during the oxidation of GSH by HOCl (and a minor species for other oxidants) exhibits a molecular mass that is 30 mass units heavier than GSH. This GSH+2O-2H species, which has been employed as a biomarker for oxidative stress, has been previously proposed to be a sulfonamide. Employing NMR spectroscopy and mass spectrometry, we demonstrate that the GSH+2O-2H species is indeed a nine-membered cyclic sulfonamide. Alternative formulations, including six-membered 1,2,5-oxathiazine heterocycles, have been ruled out. Remarkably, the sulfonamide exists as a 2:1 equilibrium mixture of two diastereomers. Isotope tracer studies have demonstrated that it is the Glu C alpha center that has undergone racemization. It is proposed that the racemization takes place via an acyclic imine-sulfinic acid intermediate. The glutathione sulfonamides are stable products of GSH that have been detected in physiological systems. Elucidation of the structures of the glutathione sulfonamides provides further impetus to explore their potential as biomarkers of hypochlorous acid formation.

ChemInform Abstract: Novel 1β‐Methylcarbapenems Having Cyclic Sulfonamide Moieties: Synthesis and Evaluation of in vitro Antibacterial Activity.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Novel lβ-methylcarbapenems having cyclic sulfonamide moieties: Synthesis and evaluation of in vitro antibacterial activity

The synthesis of a new series of 1β-methylcarbapenems having cyclic sulfonamide moieties is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituent on the pyrrolidine ring was investigated. A particular compound ( IIIi) having 2-methyl-[1,2,6]thiadiazinan-1,1-dioxide moiety showed the most potent antibacterial activity.

The Double Reduction of Cyclic Sulfonamides for the Synthesis of (4S-Phenylpyrrolidin-2R-yl)methanol and 2S-Methyl-4S-phenylpyrrolidine

The synthesis of (4S-phenylpyrrolidin-2R-yl)methanol and 2S-methyl-4S-phenylpyrrolidine has been achieved via the double reduction of their cyclic sulfonamide precursors which themselves were prepared following the stereoselective intramolecular Heck reaction of a chiral pool derived 2,5-dihydropyrrole. We have recently described a process whereby cyclic aryl sulfonamides, such as 2, are reductively ring-opened to furnish amino products in which the aryl group is incorporated in the final compound. (Evans, P.; McCabe, T.; Morgan, B. S.; Reau, S. Org. Lett. 2005, 7, 43.) The precursors for this reaction were assembled using an intramolecular Heck reaction followed by reduction of the alkene. Overall, this sequence represents an efficient means to construct molecules of this type in which the aryl sulfonyl moiety acts as both an N-protecting group and as an aryl donor. Use of Benkeser's stronger reducing conditions enables molecules such as 4 to be prepared in which both the sulfonamide functional group and the aromaticity of the aryl substituent have been destroyed.

Optimization of a privileged structure leading to potent and selective human melanocortin subtype-4 receptor ligands

Design and synthesis of potent MC4 selective agonists based on cyclohexylpiperidine derived cyclic urea, oxazolidinones, and sulfonamide based privileged structures are disclosed.

Acetylenic TACE Inhibitors. Part 2. SAR of Six‐Membered Cyclic Sulfonamide Hydroxamates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates

The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1′ group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-α production and a collagen-induced arthritis model.

Synthesis of cyclic peptidosulfonamides as scaffolds for MC4 pharmacophoric groups

The synthesis of potential β-turn mimetics based on cyclic sulfonamide peptoid/peptoid hybrids is described. These are readily synthesized using a solid phase protocol followed by cyclization in solution, and their suitability to combinatorial approaches is illustrated by the synthesis of a small but diversely functionalized library.

Sultam and Sultim Structures, Part 2. Functionalized Novel Cyclic Sulfin- and Sulfonamides: A Comparison of Hydrogen Bonding Formation in Sulfoxides and Sulfones

The stable hydroperoxides rac-cis-2a,d and 4a,c were synthesized by oxidation of the salts 1. The 3-hydroxy sultims rac-cis-3a,b and sultams 5a,e were obtained by reduction of the corresponding hydroperoxides 2 and 4. Crystal structure analyses were performed for compounds 3b, 4a, 5a, 5e and revealed a variety of intermolecular contacts leading to cyclodimers, tetramers and polymers. In carboxylic esters 4a and 5a, cyclodimers with a 20- or 22-membered ring are formed via ‘head-to-tail’ CO⋯H-O hydrogen bonds and π/π-interactions, without participation of the SO2 group. The 1,1-dioxide 4c, which has no carbonyl substituent, forms a tetrameric unit by combining two symmetry independent molecules through strong OO-H⋯O-S-O and short nonclassical O-S-O⋯H-C hydrogen bonds. The sultam 1,1-dioxide 5e, bearing a highly substituted 2-phenyl ring, exhibits in the solid state strong intermolecular O-S-O⋯H-O hydrogen bonds and forms the first polymer chain in this cyclic sulfonamide series. In sultims 2a, 3a and 3b, but not in 2d, strong intermolecular S-O⋯H-O hydrogen bonds are observed and polymer chains originate from the c-glide plane (space group P21/c)in 2a and from two symmetry independent molecules in 3a. In the 1-oxide 2d a ‘head-to-head’ dimer was found with two strong SO⋯H-OO hydrogen bonds in a 14- or 16-membered ring. Short nonclassical C-H⋯O-C interactions connect the dimers to form polymeric chains.

Glutathione Oxidation by Hypochlorous Acid in Endothelial Cells Produces Glutathione Sulfonamide as a Major Product but Not Glutathione Disulfide

Treatment of cells with hypochlorous acid (HOCl) at sublethal doses causes a concentration-dependent loss in reduced glutathione (GSH) levels. We have investigated the products of the reaction of HOCl with GSH in human umbilical vein endothelial cells. Despite a complete loss of GSH, there were only very small increases in intracellular and extracellular glutathione disulfide and glutathione sulfonic acid after exposure to HOCl. (35)S labeling of the GSH pool showed only a minimal increase in protein-bound GSH, suggesting that S-thiolation was not a major contributor to HOCl-mediated loss of GSH in endothelial cells. Rather, the products of the reaction were mostly exported from cells and included a peak that co-eluted with the cyclic sulfonamide that is a product of the reaction of GSH with reagent HOCl. Evidence of this species in endothelial cell supernatants after HOCl treatment was also obtained using electrospray mass spectrometry. In conclusion, exposure to HOCl causes the irreversible loss of cellular GSH with the formation of novel products that are rapidly exported from the cell, and resynthesis of GSH will be required to restore levels. The loss of GSH would alter the redox state of the cell and compromise its defenses against further oxidative stress.

ChemInform Abstract: Ring Enlargement of Eight‐ and Nine‐Membered Cyclic Sulfonamide Derivatives in Reactions with 3‐Amino‐2H‐azirines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ring Enlargement of Eight- and Nine-membered Cyclic Sulfonamide Derivatives in Reactions with 3-Amino-2H-azirines

The reactions of 3-dimethylamino-2H-azirines (1) with 3,4,5,6-tetrahydro-8,9-dimethoxy-2H-1,2-benzothiazocin-3-one 1,1-dioxide (6a) in acetonitrile gave the correspondingly substituted 3-dimethylamino-4,5,6,7,8,9-hexahydrobenzo-1-thia-2,5-diazacycloundecen-6-one 1,1-dioxides (8). In the case of the reaction of 1a with 6a, the 3-amino-5,6-dihydro-4H-benzothiazocine 1,1-dioxide derivative (9) was formed as a minor product. The structures of the starting material (6a), the unexpected 4,5-dimethoxy-2-(3-cyanopropyl)benzenesulfonyl chloride (7), the novel eleven-membered heterocycles (8a,8c) and that of 9 were established by X-Ray crystallography. With the nine-membered homologue 2,3,4,5,6,7-hexahydro-9,10-dimethoxy-1,2-benzothiazonin-3-one 1,1-dioxide (6b), only the most reactive aminoazirine yielded the ring enlarged twelve-membered heterocycle (10).

Vinyl sulfonyl esters and amides in the synthesis of substituted .delta.-sultams and .delta.-sultones

The Michael reaction of phenyl vinyl sulfonate (3) or vinyl sulfonamide 12 with phenylacetic esters was the key step in a general synthesis of 4-phenyl-substituted 1,2-thiazane 1,1-dioxides (sultams) and 5-phenyl-1,2-oxathiane 1,1-dioxides (sultones). This methodology was applied to the synthesis of some cyclic sulfonamide and sulfonate derivatives (I and II) of the potent TXA 2 receptor antagonists BM.13177 and BM.03505