Sulphonamide Group Research Articles

Kinetics of desulphonative double Smiles' rearrangement of N-(2-hydroxyalkyl)-p-nitrobenzenesulphonamides

Support for a mechanism of formation of N-(2-hydroxyethyl)-p-nitroanilines by base-catalysed desulphonation of N-(2-hydroxyethyl)-p-nitrobenzenesulphonamides has been obtained by kinetic investigation. Derivatives bearing alkyl and aryl substituents on nitrogen, or C-alkyl substituents α- or β- to the hydroxy-group have also been studied. Substituent effects on the rate and base dependence of (i) intramolecular aromatic displacement of the sulphonamide group by the neighbouring hydroxy-group and (ii) rearrangement of the intermediate 2-(p-nitrophenoxy)alkylamine have been determined for this double Smiles' rearrangement sequence. Intermediate aminoethers have been detected spectroscopically for the first time and have in some cases been isolated.

Exchange of Sulphonamide Group in a Halogen

Abstract It is well known, that the addition of a halogen to the alkaline solution of an aryl sulphonamide yields the corresponding salt of N-halosulphonamide and then N,N-dihaloderivative. Temperatures of 50–60° are usually used.

Determination of chloramine T in dairy products.

A method has been developed for the quantitative determination of traces of chloramine T (Activin, Halamid) in dairy products. Proteins are removed and the hydrolysis product toluene-4-sulphonamide is extracted with ether. After evaporation of the solvent, the residue is oxidized with an alkaline potassium permanganate solution. The oxidized product is isolated by ether extraction and the residue is subjected to reduction with Raney Nickel catalyst in a sodium hydroxide solution. The sulphonamide group is split off and the benzoic acid thus formed is subjected to a gas chromatographic analysis.

The crystal and molecular structure of benzenesulphonamide-p-(tetrahydro-2H-1,2-thiazin-2-yl)-S,S-dioxide

Crystals of benzenesulphonamide-p-(tetrahydro-2H-1,2-thiazin-2-yl)-S,S-dioxide, Sulthiame, are orthorhombic, space group Pca2,, with a= 8.250 (3), b= 17.713 (7), c= 8.638 (3)/~. The structure has been refined to R=0.063 for 710 independent reflexions measured on an automatic four-circle diffractometer. The heterocyclic ring adopts the chair conformation and the basal plane of the chair makes a dihedral angle of 121.0 ° with the plane of the aromatic ring. Hydrogen bonds between the sulphonamide groups connect the molecules in layers parallel to (010).

Affinity labelling of proteinases with tryptic specificity by peptides with C-terminal lysine chloromethyl ketone.

Methods are described for the synthesis of peptides terminating in Lys-CH(2)Cl. The products were examined as affinity labels for several enzymes of trypsin-like specificity which are resistant to Tos-Lys-CH(2)Cl. In part, the inertness of the latter may be due to the sulphonamide group, since Z-Lys-CH(2)Cl was more effective. However, a number of tripeptides with C-terminal Lys-CH(2)Cl were superior in their ability to inactivate subtilisin, thrombin and plasma kallikrein. The possibility of developing enzyme-specific reagents selective for members within the trypsin-like group is demonstrated by Ala-Phe-Lys-CH(2)Cl, which readily inactivates plasma kallikrein but not thrombin.

Acute response of the mouse bladder to derivatives of 4-ethylsulphonylnaphthalene-1-sulphonamide and bladder carcinogens measured by the uptake of [ 125I]5-iodo-2′- deoxyuridine

The structural features of 4-ethylsulphonylnaphthalene-1-sulphonamide (ENS) responsible for the induction of DNA synthesis in the mouse bladder have been investigated using a method in which DNA synthesis is measured by the uptake of a thymidine analogue, [ 125I]5-iodo-2′-deoxyuridine (IUdR). The ability to stimulate DNA synthesis was unaffected by the nature of the alkyl group in 4-alkylsulphonylnaphthalene-1-sulphonamide. The sulphonamide group appeared to be essential to the activity of the molecule because naphthalene-1,4-disulphonamide was active whereas 1,4-diethylsulphonylnaphthalene was not. Maximum activity was found when the sulphonamide group was attached to an aromatic system (benzene or naphthalene) containing an alkylsulphonyl or a sulphonamide group. Bladder carcinogens other than ENS failed to stimulate the uptake of [ 125I]IUdR sufficiently to produce statistically significant results. The reasons for the large variation in response between individual mice are discussed, as are the implications of the structure activity relationships to the mode of action of ENS.

Crystal structure studies on human erythrocyte carbonic anhydrase C. (II)

Several heavy-atom derivatives of human carbonic anhydrase form C have been prepared. Mercury atoms have been placed in at least four different sites. Two of the heavy-atom derivatives were obtained using sulphonamide inhibitors. The zinc atom, necessary for enzyme activity, has been removed and replaced by a mercury atom by means of reactions in the enzyme crystals. The positions of the heavy atoms and degrees of substitution in these positions were refined by a least squares procedure. For all derivatives, the mercury content found by X-ray investigation has been correlated with the values obtained by activation analyses. By using the native enzyme and four different isomorphous heavy-atom derivatives, X-ray analysis has led to an electron density projection of the unit cell of the protein. The same derivatives will be used to determine the three-dimensional structure of the enzyme (this work is in progress to 5.5 Å resolution). Chemical and crystallographical evidence has led to approximate positions of the zinc atom and of the only SH-group in the enzyme molecule. The minimum Zn-S distance is 10 Å. In sulphonamide derivatives one small electron density peak (probably a sulphonamide group) is situated close to the zinc position.

Some Interactions of Anionic Dyes used in Medical and Biological Research and Teaching

Many anionic dyes are amphoteric because they contain basic side‐chains. Such dyes are really artificial amino acids. A large number of polyanionic dyes have been isolated and synthesised in vitro by interactions of simple anionic dyes. These complex dyes are, in effect, artificial peptides or simple synthetic proteins. Structural examples show their molecules to contain sulphonamide or disulphonamide groups. Some of these complex dyes have found useful application (e.g. trifalgic acid in diagnostic pathology; Haplo and Haplos in polarising microscopy9 and cytology). Certain anionic dyes act as decolorising agents towards other dyes, a fact that may be of importance in textile dyeing. A more rational system of dye classification is proposed to supplement the traditional systems commonly used.

Review of 8,000 cases of pneumonia admitted to Dudley Road Hospital, Birmingham (1934-38 and 1944-48).

This study was initiated primarily to discover what use could be made of routine medical records kept in a large general hospital. The Dudley Road Hospital, Birmingham, has for many years main tained a diagnostic index which records the following facts for each discharge or death: diagnosis, age, sex, dates of admission and discharge, complications, disposal, and case reference number. Attention was focused on admissions referable to pneumonia because it is one of the commonest reasons for hospital admission, and methods of treatment have changed dramatically during the past 15 years. The inquiry takes within its scope records of two quin quennia, 1934-38 and 1944-48; these were chosen because: (a) sulphonamide therapy was not yet in general use during the first period; (b) singly or jointly, drugs of the sulphonamide group and antibiotics had become the standard treatment for cases of this sort during the second period. The ensuing study is not in the fullest sense of the term a since it was not feasible to ensure matching of cases with regard to conditions relevant, or possibly relevant, to treatment efficacy. None the less, it should be illuminating if only as a historical review of the treatment of the pneumonia over the last two decades. The historical control (Hill, 1951; Hogben and Wrighton, 1952) has admittedly and rightly been a target of criticism; but it may happen to be the only method of comparison feasible in a field in which ethical as well as practical difficulties beset the theoretically desirable task of subjecting the use of every new drug to a rigorously controlled experiment. Such difficulties are often surmountable when a new drug is available at first only in very small quantities. In such a situation, selection of test cases is inevitable, and the dictates of the ideally controlled clinical trial confront the

Fixed eruption due to sulphonamide hypersensitivity.

Cutaneous reactions following the use of the sulphonamide group of drugs are of not uncommon occurrence. Fixed eruptions due to these drugs are comparatively rare. Robson and Keele (1950) define a fixed eruption as being characterized by the rapid development of one or more sharply circumscribed lesions on the skin or mucous membranes, as an invariable response to the administration of the offending drug . As sulphonamides are still used on a limited scale in the treatment of venereal diseases, the following cases are considered of sufficient interest to merit publication.

Salinogenic or chelate forming dyes as analytical reagents

AbstractThe diazoaminogroup (—N=N·NH—) was found to be silver, mercury and cadmium selective. The sulphonamide group (—SO2·NH—) as present in sulphanilamide and other sulpha drugs is similarly reactive. Para diethylaminobenzeneazo chromotropic acid (“chromotropic blue”) was found to be cerium, calcium, magnesium and under certain conditions copper, nickel and cobalt selective. Copper specific and nickel‐selective, is 5‐(p‐nitrobenzeneazo)‐7‐nitroso‐8‐hydroxyquinoline (“oxin violet”). New reactions of nitroso‐R‐acid and photographic reactions of some of the mentioned chemicals are described.

The synergic action of penicillin and sulphathiazole onS. typhi

Due to earlier reports of the relative resistance ofS. typhiand other members of the salmonella group to penicillin, and to the prevalent preoccupation of most workers with those organisms against which treatment with penicillin was more obviously applicable, little attention was payed to the chemotherapy of enteric fever until Bigger (1946) published his findings on the synergic action of a more reliable guide to the occurrence of synergism than sterilization, might be demonstrated. In conformity with the previous results, however, treated broth was also used to demonstrate synergic killing effect. Results are given in Table 12.T455, when tested under similar conditions, was inhibited by 6·25 u./ml. penicillin and showed a twofold inhibitory synergism in the presence of sulphathiazole. It will be seen that all the strains tested showed some degree of inhibitory synergism but that, in the majority, the concentration required to inhibit growth was considerably higher than in the case ofS. typhi. With the majority of strains the concentration of penicillin required to destroy the inoculum in 24 hr. at 37° C. was greater than 25 u./ml., even in the presence of sulphathiazole, while in one case no bactericidal synergism at all penicillin and sulphathiazole againstS. typhi. Although, therefore, much work has been published concerning the synergic action of the sulphonamide group on penicillin activity in general, little information is available on thein vitrobehaviour of the salmonellas in this respect despite the present wide, though tentative, application of the principle in the treatment of enteric fever. The experiments presented above were undertaken with the object of confirming those findings hitherto reported and of studying in detail the effects of sulphathiazole and penicillin, and of combinations of the two, on the salmonella group, with special reference toS. typhi.For purposes of discussion it is convenient to summarize our results under the principal headings used in the text.

Le globucid (n. d.) essais d' identité et dosages

This analytical study of Globucid (sulphanilaminoethylthiodiazole) comprises : l. The determination of physical constants, melting-point and solubilities, of the compound. 2. The identification of the different functional groups, arylamine, substituted benzene, sulphonamide and tests for aminoethylthiodiazole by colour and precipitation reactions, as well as a number of precipitation and microchemical reactions of Globucid itself. 3. A quantitative section : determination of total nitrogen and thiodiazole nitrogen by difference, determination of amino nitrogen, acidimetric and argentometric determination of the sulphonamide groups, determination of total sulphur and thiodiazole sulphur and finally bromometric assay of Globucid.

Carbonic Anhydrase, Sulphonamides and Shell Formation in the Domestic Fowl

Meldrum and Roughton1 were the first to advance the hypothesis that carbonic anhydrase might play a part in egg-shell formation by influencing the rate of formation of the anion of calcium carbonate by catalysis of the reaction CO2 + H2O = H2CO3. Following up this suggestion, Common2 examined the tissues of the hen's oviduct for their carbonic anhydrase activity, and concluded "that the carbonic anhydrase activity of the uterine epithelium is higher than that of the remaining oviducal tissues, and that this activity may play a part in shell secretion". On the other hand, it has been demonstrated by Keilin and Mann3 that compounds of the RSO2NH2type (where R is a benzene, naphthalene or pyridine ring) specifically inhibit carbonic anhydrase in very small concentrations. This property, however, is absent in all such compounds in which the sulphonamide group is substituted, as it is, for example, in sulphapyridine or sulphathiazole.

Bacterial chemotherapy, III: Synthesis of possible lipophilic chemotherapeuticals of the sulphanilamide group

On the ground that the sulphonamide group of drugs after suitable synthetic modifications of their molecules may probably be useful in mycobacterial infections, the possibility of rendering a few members, previously known to be active in coccal infections, lipophilic by the introduction of fatty acid residues in the latter has been explored. Accordingly, normal and branched chain acyl derivatives, thirty-seven in all, of sulphanilamide, sulphapyridine, sulphathiazole, sulphathiazoline, etc., have been synthesised.

The Use of the Sulphonamide Group of Drugs in the Treatment of Tonsillitis due to the Beta-Haemolytic Streptococcus and in Acute Rheumatic Fever

The Use of the Sulphonamide Group of Drugs in the Treatment of Tonsillitis due to the Beta-Haemolytic Streptococcus and in Acute Rheumatic Fever

MODE OF ACTION OF DRUGS OF THE SULPHONAMIDE GROUP

Medical Journal of AustraliaVolume 1, Issue 17 p. 660-661 Current Comment MODE OF ACTION OF DRUGS OF THE SULPHONAMIDE GROUP First published: 01 April 1939 https://doi.org/10.5694/j.1326-5377.1939.tb114707.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume1, Issue17April 1939Pages 660-661 RelatedInformation

Notes on the Treatment of Gonorrhœa with the Sulphonamide Group of Drugs

Notes on the Treatment of Gonorrhœa with the Sulphonamide Group of Drugs

Abscess of the lung: A clinical study

(1) Clinical, radiological, and bacteriological studies of thirty-two cases of abscess of the lung, are reviewed. (2) It is interesting to note that all but two of them are abscesses of unknown aetiology. (3) It is suggested that some cases might have started as the ‘disseminated focal pneumonia’ of Scadding. (4) Pain as a prominent symptom is noted. (5) Medical treatment should be given a fair chance in all acute cases. (6) The sulphonamide group of drugs gave very promising results in the few cases tried.