Sulfonamides release

Alkylation of oxazoles, or imidazoles carrying, for example, a phenylsul-fonyl group on nitrogen, is more difficult, requiring methyl triflate or a Meerwein salt for smooth reaction. Subsequent simple alcoholysis of the imida-zolium-sulfonamide releases the A -substituted imidazole. Moreover, since acylation of 4(5)-substituted imidazoles gives the sterically less crowded 1-acyl-4-substituted imidazoles, subsequent alkylation, then hydrolytic removal of the acyl group, produces 1,5-disubstituted imidazoles. ... 

The use of images in terms of oxidized developer to release dyes initially immobilized through a sulfonamide linkage has been described (33). In one approach color coupling leads to ting closure and concomitant release of an alkah-soluble dye (eq. 1). 

A second approach utilizes the oxidation of alow mobiUty substituted 4-hydroxydiphenylamine to which an image dye is linked through a sulfonamide group. Oxidation and hydrolysis result in ting closure and release of the alkaU-soluble dye (eq. 2). 

As an extension to thep-carboxybenzenesulfonamide safety-catch linker [43,44], alkanesulfonamide handle 37 was developed [45]. This linker tethers carboxylic acids to the solid support to give an acylated sulfonamide which is stable to both basic and acidic conditions (Scheme 12). Products were released by treatment with iodoacetonitrile followed by the addition of a nucleophile. 

A-Protected amines were assembled on solid-phase via sulfonamide-based handle 58 (Scheme 27) [67]. Tertiary sulfonamides were generated upon reaction with allylic, benzylic and primary alcohols under Mitsu-nobu conditions. Secondary amines were released from the support using mild nucleophilic conditions such as treatment with thiophenol and potassium carbonate. 

Zonisamide is a broad-spectrum sulfonamide AED that blocks voltage-sensitive sodium channels by reducing voltage-dependent T-type Ca channels it also weakly inhibits carbonic anhydrase, and inhibits glutamate release. 

The instability of primary nitramines in acidic solution means that the nitration of the parent amine with nitric acid or its mixtures is not a feasible route to these compounds. The hydrolysis of secondary nitramides is probably the single most important route to primary nitramines. Accordingly, primary nitramines are often prepared by an indirect four step route (1) acylation of a primary amine to an amide, (2) A-nitration to a secondary nitramide, (3) hydrolysis or ammonolysis with aqueous base and (4) subsequent acidification to release the free nitramine (Equation 5.17). Substrates used in these reactions include sulfonamides, carbamates (urethanes), ureas and carboxylic acid amides like acetamides and formamides etc. The nitration of amides and related compounds has been discussed in Section 5.5. 

Slow release drugs, 143 Solifpertine, 342 Sotalol, 41 Soterenol, 40 Spirilene, 292 Spi2 onolactone, 172 Stenbolone acetate, 155 Strecker reaction, 119 Streptokinase, 377 Sudoxicam, 394 Sulazepam, 403 Sulfabenzamide, 112 Sulfacytine, 113 Sulfanilamide, 112 Sulfanitran, 115 Sulfapyridine, 114 Sulfasalazine, 114 Sulfazamet, 113 Sulfonamide diuretics,... 

Silver sulfadiazine, a sulfonamide, is used for the management of infected burns. The occurrence of sulfonamide hypersensitivity is a serious risk though and this agent should be reserved for selected cases. Its activity is probably based on the bactericidal action of silver which is released but absorbed only to a negligible extend. The sulfonamide is well absorbed and appreciable blood levels are reached when large areas are treated. 

Resistance to the sulfonamides can be the result of decreased bacterial permeability to the drug, increased production of PABA, or production of an altered dihydropteroate synthetase that exhibits low affinity for sulfonamides. The latter mechanism of resistance is plasmid mediated. Active efflux of the sulfonamides has also been reported to play a role in resistance. The inhibitory effect of the sulfonamides also can be reversed by the presence of pus, tissue fluids, and drugs that contain releasable PABA. 

Some compounds are stored in the body in specific tissues. Such storage effectively removes the material from circulation and thus decreases the toxicity of the compound. Repeated doses of a toxic substance may be taken up and subsequently stored without apparent toxicity until the storage receptors become saturated then toxicity suddenly occurs. In some cases, the stored compound may be displaced from its storage receptor by another compound that has an affinity for the same receptor. Examples of this phenomenon are the displacement of antidiabetic sul-fonylureas by sulfonamides and the ability of antimalarial drugs such as quina-crine (atabrine) and primaquine to displace each other (Loomis, 1978). A special danger in such cases is that compounds may have escaped detoxifying metabolism while stored in the body, and that their toxicity may be potent and prolonged when released. 

Methenamine mandelate, 1 g four times daily, or methen-amine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to suppress, not treat, urinary tract infection. Acidifying agents (eg, ascorbic acid, 4-12 g/d) may be given to lower urinary pH below 5.5. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites. 

Several different types of linker have been developed that yield amides upon cleavage. These linkers can often also be used to prepare sulfonamides, carbamates, or ureas. There are essentially three different strategies for the release of amides from insoluble supports (a) cleavage of the benzylic C-N bond of resin-bound N-alkyl-N-benzylamides (backbone amide linkers, BAL linkers), (b) nucleophilic cleavage of resin-bound acylating agents with amines, and (c) acylation/debenzylation of resin-bound /V-benzyl-/V,A -dialkylamines. 

A series of special linkers and cleavage strategies has been developed for the release of amines from insoluble supports (Table 3.23). These include the attachment of amines as triazenes, enamines, aminals, amidines, sulfonamides, sulfinamides, hydrazines, or amides. 

A related and more sensitive method makes a sulfonamide of the terminal NH2 group with a reagent called dansyl chloride. As with 2,4-dinitrofluorobenzene, the peptide must be destroyed by hydrolysis to release the N-sulfonated amino acid, which can be identified spectroscopically in microgram amounts ... 

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