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At least 343 records · Page 19Linked to original sources

PubMed2004

Ring-closing metathesis: development of a cyclisation-cleavage strategy for the solid-phase synthesis of cyclic sulfonamides.

A series of novel 7-membered cyclic sulfonamides have been synthesised using a solid-phase cyclisation-cleavage RCM strategy. Model solution studies indicated the sulfonamides were suitable substrates for RCM using the Grubbs' catalyst 2. Starting from either 2-carboxyethyl polystyrene (21) or Merrifield resin, various seven-membered sulfonamides were prepared in good to excellent yields at low catalyst loadings (2.5-5 mol%) using a flexible spacer between the polymer and the substrate. In addition, a novel double-armed linker was shown to allow efficient RCM cleavage of sulfonamides with as little as 1 mol% of the ruthenium alkylidene complex 2.

Journal Article↗

PubMed1989

Ocular hypotensive activity and disposition of the topical carbonic anhydrase inhibitor 6-hydroxy-benzo[b]thiophene-2-sulfonamide, L-650,719, in the rabbit.

The carbonic anhydrase (C.A.) inhibitor, L-650,719 (6-hydroxy-benzo[b]thiophene-2-sulfonamide) is an advance over the corresponding 6-OH benzothiazole-2-sulfonamide in increased water solubility (4 mM) and CHCl3/buffer partition (0.05). KI vs CA is 10(-8) M. Topical treatment with 1 drop of 0.15-8% suspensions (in hydroxyethylcellulose-HEC) lowered intraocular pressure (IOP) up to 2.6 mmHg, with a plateau at 2%. Two hours after 2% treatment ocular drug distribution showed (microM or mumole/kg): cornea, 115, anterior aqueous 27, posterior aqueous 4, ciliary processes 15. Calculated inhibition of C.A. is 99.7%. IOP lowering effect disappeared at 6 hrs. L-650,719 was also given in solution (17 mM, pH 9.3). One drop every 5 min x 5 or 10 min residence on cornea of this solution produced an IOP lowering and drug distribution similar to that of the 2% suspension. Increasing HEC concentration in the single drop solution from 0 to 1%, led to a 3-fold increase in anterior aqueous drug levels and an improved delta IOP. The pressure lowering is somewhat less than achieved with parenteral sulfonamides in the rabbit. Clinical trials showed modest activity, so L-650,719 is not being developed further. It is evident, however, that sulfonamides with a variety of chemical and pharmacological properties are conducive to development for topical treatment of glaucoma.

Animals↗

PubMed1979

Characterization of mutationally altered dihydropteroate synthase and its ability to form a sulfonamide-containing dihydrofolate analog.

Among spontaneous mutants of Escherichia coli selected for resistance against sulfonamides, thermosensitive strains were found. These were shown to possess a changed dihydropteroate synthase (EC 2.5.1.15), which had a substantially higher Km value for its normal substrate, p-aminobenzoic acid, and an about 150-fold higher Km for sulfonamides. The mutationally changed dihydropteroate synthase was found to be thermosensitive by in vitro assays. The thermosensitivity was used as an enzyme marker to demonstrate the complex formation between 2-amino-4-hydroxy-6-pyrophosphorylmethyl pteridine and sulfonamides by partially purified dihydropteroate synthase. The formation of folate from 2-amino-4-hydroxy-6-pyrophosphorylmethyl pteridine and p-aminobenzoylglutamic acid by dihydropteroate synthase was found to be very sensitive to inhibition by sulfonamides and very inefficient with the mutationally changed enzyme.

4-Aminobenzoic Acid↗

PubMed1999

Carbonic Anhydrase Inhibitors. Synthesis of Topically Effective Intraocular Pressure Lowering Agents Derived from 5-(omega-Amino- alkylcarboxamido)-1,3,4-Thia- diazole-2-Sulfonamide.

Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and deprotection of the phthalimido group the corresponding 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta-aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or acyl halides afforded a series of compounds possessing beta-alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play an important role in aqueous humor secretion within the ciliary processes of the eye. Some of the synthesized inhibitors possessed good water solubility (as hydrochlorides or sodium salts) and were applied as 2% solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them for prolonged periods of 1-2 h, and the active drug was detected in eye tissues and fluids indicating that the antiglaucoma effect is due to CA inhibition within the eye.

Journal Article↗

PubMed1989

Tissue sulfonamide concentration and correlation in turkeys.

Nineteen hen turkeys (10 to 12 kg each) were used in a feeding study to determine sulfadimethoxine and sulfaquinoxaline concentrations in blood serum, liver, and skeletal muscle, as well as the respective ratios at selected withdrawal intervals. Two feeds were prepared by use of premixes to achieve 60 mg of sulfadimethoxine/kg and 100 mg of sulfaquinoxaline/kg, respectively. Each of the medicated feeds was given to 9 turkeys for 7 days. The turkeys were then fed nonmedicated feed at intervals from 24 to 56 hours and were slaughtered. One turkey was used as control. The serum/liver and serum/muscle ratios for sulfaquinoxaline were 60 to 70% higher than for sulfadimethoxine. However, the liver/muscle ratio for both sulfonamides was equivalent, approximately 3. Disposition of both sulfonamides approximated first-order pharmacokinetics. The calculated half-life of sulfadimethoxine was half that of sulfaquinoxaline, approximately 16 vs 30 hours. The coefficients of variation in the serum/tissue ratios for both sulfonamides were between 13% and 25% for serum/liver and less than 15% for serum/muscle, indicating excellent potential for using serum as a predictor of actionable concentrations of sulfonamide residues.

Animal Feed↗

PubMed1982

Inhibition of homocysteine sulfonamide of glutamate synthase purified from Saccharomyces cerevisiae.

Glutamate synthase, isolated in apparently homogeneous form (Mr approximately 265,000) from Saccharomyces cerevisiae after 7500-fold purification, is markedly inhibited by homocysteine sulfonamide. Inhibitions competitive with respect to L-glutamine; the apparent Ki value calculated for L-homocysteine sulfonamide is 3.6 microM; the apparent Km value for L-glutamine is 280 microM. The very high affinity of the inhibitor for the enzyme, as well as structural considerations, suggest that homocysteine sulfonamide is a transition state inhibitor. The previously reported growth inhibitory properties of homocysteine sulfonamide (Reisner, D. B. (1958) J. Am. Chem. soc. 78, 5102-5104) may be due, at least in part, to inhibition of glutamate synthase. L-Methionine sulfone is also a potent competitive inhibitor, whereas L-albizziin, L-methionine-SR-sulfoximine, and L-methionine-SR-sulfoxide are much less effective inhibitors. S. cerevisiae glutamate synthase, which is composed of two dissimilar subunits, uses NADH exclusively, and exhibits low but definite activity when NH3 is substituted for glutamine.

Chemical Phenomena↗

PubMed2000

Regioselective template synthesis, X-ray structure, and chiroptical properties of a topologically chiral sulfonamide catenane.

The synthesis of a topologically chiral in,out-bis-sulfonamide catenane and its "dimer" are reported. The structures of the amide wheel and of the catenane were resolved by X-ray analysis. NMR-titration of the monosulfonamide-wheel yielded conclusive association constants supporting the proposed regioselective mechanism of the catenane formation. The enantioseparation of the catenane via chiral HPLC was successful. The enantiomers show pronounced Cotton effects in the aromatic region of the CD-spectrum. Since the template synthesis was carried out leading to the in-oriented sulfonamide-wheel blocked with an N-methyl group at its reactive sulfonamide functionality, the catenane represents the first monofunctional topologically chiral amide-based catenane. Reaction with 1,2-bis(2-iodoethoxy)ethane led to a bis-catenane containing two topological units. The meso- and the RR/SS-isomers represent a new type of topological diastereomers.

Chromatography, High Pressure Liquid↗

PubMed1997

Synthesis of vinca alkaloids and related compounds. Part 84. Sulfonamide derivatives of some vinca alkaloids with cardiovascular activity.

(+)-Vincamine (1) and (+)-vinpocetine (2) were chlorosulfonylated and the resulting sulfonyl chloride isomers (3-6) were transformed into sulfonamides (7-10). The ester group of sulfonamides was modified by selective hydrolysis and transesterification. Apovincaminol derivatives (14-16) were also prepared by reduction. In addition to the known cerebrovascular effects of the unsubstituted compounds (1,2) sulfonamides also show a significant peripheral vasodilator effect.

Animals↗

PubMed1996

Comparisons of oxidative metabolism and reductive capacity in sulfonamide-tolerant and -intolerant patients with human immunodeficiency virus.

Hypersensitivity reactions to trimethoprim/sulfamethoxazole occur with a high frequency in human immunodeficiency virus (HIV)-infected patients. This study tested whether differences in oxidative metabolism and plasma reductive capacity correlate with sulfonamide intolerance in patients with HIV. Eighteen stable outpatients with HIV were prospectively studied. Nine patients had documented histories of hypersensitivity reactions to trimethoprim/sulfamethoxazole and nine did not. Urinary caffeine metabolite ratios assessed the activity of two oxidative enzymatic pathways: cytochrome P-450 1A2 (demethylation) and 8-hydroxylation. Plasma cyst(e)ine was used as a measure of reductive capacity. The trimethoprim/sulfamethoxazole-intolerant group showed greater rates of 8-hydroxylation, lower rates of demethylation, and lower cyst(e)ine levels. The results of this pilot study extend previous observations of differences in oxidative metabolism and reductive capacity that exist within the population of HIV-infected individuals. In addition, these findings lay the groundwork for future interventional studies that could use agents to inhibit sulfonamide oxidation and increase reductive capacity in sulfonamide-intolerant patients with HIV when rechallenged with trimethoprim/sulfamethoxazole.

Adult↗

PubMed1982

Analysis of oral suspensions containing sulfonamides in combination with erythromycin ethylsuccinate.

The sulfonamides and erythromycin ethylsuccinate in combination oral suspensions were determined by high-performance liquid chromatography and automated turbidimetry, respectively. The chromatographic procedure was rapid, specific, and stability-indicating for sulfisoxazole acetyl and the trisulfapyrimidines using a reversed-phase system with UV detection at 254 nm. Erythromycin ethylsuccinate did not interfere with the sulfonamide analysis and these compounds were assayed with relative standard deviations (RDS) ranging from +/- 2.1 to +/- 3.1%. Erythromycin ethylsuccinate was determined as erythromycin with RSD values of +/- 1.3 or 3.5% without interference by the sulfonamides present.

Chemical Phenomena↗

PubMed1985

Extended Hildebrand solubility approach: sulfonamides in binary and ternary solvents.

The extended Hildebrand solubility approach is used to estimate the solubility of sulfonamides in binary and ternary solvent systems. The solubility of sulfisomidine in the binary solvent, dioxane-water, shows a bell-shaped profile with a solubility maximum well above the ideal solubility of the drug. This is attributed to solvation of the drug with the dioxane-water solvent, and indicates that the solute-solvent interaction energy (W) is larger than the geometric mean (delta 1 delta 2) of regular solution theory. The solubilities of sulfadiazine, sulfisomidine, sulfathiazole, and sulfamethoxazole were determined in mixtures of dimethylacetamide, glycerol, and water, and the solubility profiles were well reproduced by use of the extended Hildebrand solubility approach. Since the solubility parameter (delta 1 = 11) of the solvent (dimethylacetamide) was approximately equal to the solubility parameters of the sulfonamides, and because of the powerful solvating power of dimethylacetamide, the solubility profiles did not exhibit peaks as observed for sulfisomidine in dioxane-water. When sulfisomidine was dissolved in a ternary mixture, i.e., butyl acetate (delta 1 = 8.5), dimethylacetamide (delta 1 congruent to 11), and methanol (delta 1 = 14.5), a spike was produced in the solubility profile at the solubility parameter of dimethylacetamide. This sharply peaked profile suggests that the two branches be treated as separate solubility curves, which are then independently well reproduced by the extended Hildebrand solubility approach. None of the four sulfonamides yielded log-linear relationships in the ternary mixtures.

Acetamides↗

PubMed1988

Isoelectric points of some sulfonamides: determination by microelectrophoresis and by calculations involving acid-base strength.

The isoelectric points of four very slightly soluble sulfonamides were measured by microelectrophoresis of dilute suspensions as a function of pH. Ionic strength and pH were adjusted with KCl, KOH, and HCl only. The isoelectric points were also calculated from published values of acid and basic ionization constants which had been determined by potentiometric titration, and from changes in ultraviolet absorption spectra and in solubility as a function of pH. Including one sulfonamide whose isoelectric point as measured by microelectrophoresis was published, rather good agreement between the two methods was observed for all but one compound. All values were between 3.5 and 4.6, indicating that the sulfonamides function as weak acids rather than as amphoteric compounds at physiological pH.

Chemical Phenomena↗

PubMed1991

An evaluation of the antibacterial activities of combinations of sulfonamides, trimethoprim, dibromopropamidine, and silver nitrate compared with their uptakes by selected bacteria.

Modifications of antibacterial activity have been demonstrated using combinations of two antibacterials from trimethoprim, sulfonamides (sulfadiazine, sulfamerazine, and silver sulfadiazine), silver nitrate, and dibromopropamidine isethionate, either formulated in a cream base or dissolved in peptone water. The creams were evaluated using the agar cup diffusion method in isosensitest agar. The peptone water solutions provided fractional inhibitory concentrations for combinations of the antibacterial substances. The test organisms were Pseudomonas aeruginosa, Enterobacter cloacae, and Staphylococcus aureus. Bacterial uptakes of antibacterial combinations, determined by either an HPLC assay method or an atomic absorption method, combined with dry cell weight determinations, indicated that enhancement of activity of the antibacterial combinations against P. aeruginosa (two strains) and E. cloacae were related to marked increases in the bacterial uptake of the chemical agents. Decreases in activity were related to decreased uptake of either dibromopropamidine and/or silver ions. The effect of the trimethoprim and the sulfonamides was shown to depend on their effect on bacterial folate synthesis. It is suggested that partial blockade of the folate synthetic pathway leads to an effect on cell permeability which results in increased uptake of antibacterials. Dibromopropamidine isethionate also has an effect on cell permeability which produces an increased bacterial uptake of a second antibacterial present in the medium. These findings provide further explanation of how subinhibitory concentrations of trimethoprim and sulfonamide combinations are synergistic against a wide range of bacteria even when certain bacteria are resistant to either member of the combination.

Bacteria↗

PubMed2003

The unanticipated loss of SO2 from sulfonamides in collision-induced dissociation.

A potent and selective sulfonamide beta3 agonist with an excellent pharmacokinetic profile has recently been synthesized. During the analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS) of metabolites of the sulfonamide N-[4-[2-(2-hydroxy-2-pyridin-3-ylethylamino)ethyl]phenyl]-4-[4-(4-trifluoromethylphenyl)thiazol-2-yl]benzulfonamide (compound A), we observed loss of 64 Da for a few of the metabolites in the negative ion mode. Accurate mass measurements performed with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and quadrupole time-of-flight (Q-TOF) mass spectrometry suggested that the loss of 64 Da corresponded to the loss of SO(2). The same phenomenon was observed for a group of structurally related and commercially available compounds that also contain a sulfonamide moiety. MS/MS analysis of the fragment ions that had lost SO(2) in the ion source suggested that these ions were covalently bound rather than ion-molecule complexes. The neutral loss involving the cleavage of two bonds was unanticipated and suggested a complex rearrangement process. A mechanism for the loss of SO(2) has been proposed.

Animals↗

PubMed1984

Dermatitis herpetiformis: effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity.

The effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity were studied using in vitro assays to measure these parameters. Leukocyte iodination was documented using a quantitative assay to measure the iodination of protein by human neutrophils undergoing phagocytosis. Cytotoxicity for the tumor cell line LSTRA by human neutrophils activated by exposure to phorbol myristate acetate was measured by a 51Cr release assay. Dapsone, diasone, and sulfapyridine, at concentrations comparable to serum levels obtained by therapeutic doses of drug, effectively inhibited iodination and cytotoxicity mediated by human neutrophils. Other sulfonamides showed little inhibition of either iodination or cytotoxicity. The amount of inhibition was comparable to that seen with the inhibitors azide or cyanide and occurred in a dose dependent manner with all three drugs. A cell-free cytotoxic system using myeloperoxidase, iodide, a H2O2 generating system, and target cells also showed inhibition by dapsone, diasone and sulfapyridine in a similar fashion. The active drugs inhibited both the intra- and the extracellular myeloperoxidase-H2O2-halide cytotoxic systems. Serial iodination studies of four dermatitis herpetiformis patients, evaluated while taking dapsone or sulfapyridine, showed inhibition of iodination by either drug. Levels of IgA immune complexes, as measured by the Raji cell radioimmune assay adapted for IgA, did not change when medication was withheld. These studies demonstrate that dapsone, diasone, and sulfapyridine inhibit both neutrophil iodination and cytotoxicity for tumor cells, while other sulfonamides have no effect. This confirms previous studies showing inhibition by myeloperoxidase mediated iodination by dapsone. Furthermore, the effect on neutrophils is quickly reversible; in vivo administered drug has no effect on in vitro function. The active drugs inhibit both intra- and extracellular cytotoxic systems. This may represent an important mechanism by which these drugs produce their therapeutic effects when used to treat inflammatory skin diseases.

Antigen-Antibody Complex↗

PubMed1985

Rapid thin-layer chromatographic screening method for the detection of five sulfonamides in swine tissues: collaborative study.

A rapid thin-layer chromatographic screening method for five sulfonamides in swine tissues was studied collaboratively in nine Dutch laboratories. All collaborators were sent fifteen swine muscle and fifteen swine kidney samples. These were obtained from treated swine or from swine tissues spiked with sulfonamides at levels ranging from 0 to 0.4 mg/kg. The study indicates that the method is suitable for the screening of animal tissues for these sulfonamides. False scores occasionally occur at the lowest levels.

Animals↗

PubMed1986

[Multimethod for the determination of residues of chemotherapeutic drugs, antiparasitic agents and growth promotors in foodstuffs of animal origin. 1. General procedure and determination of sulfonamides].

Applying this Multi-Method, it is possible to isolate more than 60 chemotherapeutics, antiparasitics and growth promoters in one procedure from eggs, milk and meat. Residues are detected by different chromatographic systems (HPLC with UV-Detection, Capillary-GC with an ECD). Depending on substance and foodstuff, the following detection limits can be achieved: (Table: see text). The observance of the legal tolerance level of 0.001 mg/kg Chloramphenicol (valid only for milk and eggs in the Fed. Rep. Germany) can be supervised. Residues of most Sulfonamides can be determined to adequately, check the proposed tolerance level of 0.1 mg/kg. The first part presents the procedure (applicable for all substances) and contains the summary of the chromatographic parameters for the detection of all substances and the detailed parameters for Sulfonamides. The conformation of residues of Sulfonamides is discussed carefully.

Animals↗

PubMed1983

Dissemination of streptomycin and sulfonamide resistance by plasmid pBP1 in Escherichia coli.

About one third of streptomycin resistance in Escherichia coli is mediated by APH-(3''). This enzyme is encoded by the plasmid pBP1 in 80% of all streptomycin resistant strains tested. pBP1, which in addition mediates sulfonamide resistance, has been found to be disseminated in Escherichia coli strains all over the world. It has a molecular weight of 4.0 megadalton and does not seem to be disadvantageous for the metabolism of the bacterial cell. The reason for the slow decrease of resistance to streptomycin and sulfonamide in clinical isolates, despite the restricted use of these drugs, is presumably the survival of bacteria harbouring pBP1 which have been selected by streptomycin and sulfonamides in the early days of chemotherapy.

Anti-Bacterial Agents↗