Sulfonamides functionalities

Sulfonamides derived from sulfanilamide (p-arninoben2enesulfonainide) are commonly referred to as sulfa dmgs. Although several dmg classes are characterized by the presence of a sulfonamide function, eg, hypoglycemics, carbonic anhydrase inhibitors, saluretics, and tubular transport inhibitors, the antibacterial sulfonamides have become classified as the sulfa dmgs. Therapeutically active derivatives are usually substituted on the N nitrogen the position is generally unsubstituted. These features are illustrated by the stmctures of sulfanilamide (1) and sulfadiazine (2)... 

Nucleophilic displacement by amines and O and S nucleophiles. Subsequent access to inline, carbamate, sulfonamide functions... 

The macrolide erythromycin inhibits protein synthesis and resistance is induced by N -dimethyl-ation of adenine within the 23S rRNA, which results in reduced affinity of ribosomes for antibiotics related to erythromcin (Skinner et al. 1983). Sulfonamides function by binding tightly to chromosomal dihydropteroate synthetase and resistance to sulfonamides is developed in the resistance plasmid through a form of the enzyme that is resistant to the effect of sulfonamides. 

Although it is sometimes possible to considerably improve the fastness properties of a monoazo yellow pigment by introducing carbonamide groups or sulfonamide functions into the molecule, the applicability of a pigment is not likely to extend basically beyond its original scope. 

This hydrogen bonding capacity expressed by the polar selectivity is not limited to an increase in retention for phenols. Packings with embedded polar groups that excel in this feature also exhibit increased retention for analytes with other functional groups. Specifically, carboxylic acids at acidic pH and with acetonitrile as the organic modifier and compounds with sulfonamide functions at acidic and neutral pH exhibit significant... 

The thioxanthenes differ from the phenothiazines by the replacement of nitrogen in the central ring with a carbon-linked side chain fixed in space in a rigid structural configuration. An N,N-dimethyl sulfonamide functional... 

However, the redox potentials of the Ni(II) complexes of the aza-cyclam (3b-3g) containing carboxamide or sulfonamide functional groups are reported to be influenced by the nature of the functional group. In particular, the amide fragment controls the reduction potential for the Nim/Nin and NiI1/NiI redox couples, which may be attributed to the it interaction between the nickel ion and the amido group 14). 

Beaver, K. A. Siegmund, A. C. Spear, K. L. Application of the Sulfonamide Functional Group as an Anchor for Solid Phase Organic Synthesis (SPOS), Tetrahedron Lett. 1996,37, 1145-1148. 

The sulfonamide macrocycle proved to be a hospitable template, and at the same time the sulfonamide functionality bears the possibility of farther derivatiza-tion of [2]rotaxanes (see Section 8.4 Chemistry with Amide-Based Catenanes and Rotaxanes). Furthermore the expansion of the cavity did not afford a change of the blocking group - no disassembly of wheel and axle was detected. 

The NH groups of sulfonamide functions are also readily alkylated. The 1,2,6-thiadiazine dioxide (74) gives the 2-methyl derivative on treatment with iodomethane in acetone in the presence of potassium carbonate <65CI(L)182). The 1,3,2,4,6-dithiatriazine (75) forms a silver salt (64MI22800), and reaction of the salt with iodomethane gives the expected TV-methyl compound. 

The complex [Gd(DTPA-SA)]-, which has a sulfonamide function at the central glycine unit of DTPA has been been proposed as a CA targeting the enzyme carbon anhydrase [191]. The complex shows a strong interaction with this enzyme (K = 15,000 M-1), supposedly through the catalytic Zn2+ ion and the active site. 

In 1996 we reported on the first covalent dimerization of the [2]rotaxane with sulfonamide function in its wheel component to give a [3]rotaxane 32 (bis[2]rotaxane) [49], Subsequently, we expanded the concept of covalent bridging and produced more elaborate rotaxane assemblies such as an unsymmetrical bis[2]rotaxane 33, and 34,... 

The introduction of azobenzene units into the side chains of poly(L-lysine) has been achieved be means of various procedures and different azo reagents. The polymers described initially contained azobenzene units linked to the lysine side chains by means of an amide moiety 29-311 (Scheme 4, Structure V). More recently, Fissi et al. 321 have described azo-modified poly(L-lysine) in which the azobenzene units are linked to the Lys side chains by means of a sulfonamide function (Scheme 4, Structure VI). The two families of azo-modified poly(L-lysine) have been found to exhibit completely different conformational and photoresponsive behavior. 

Poly(L-lysine) containing azobenzene units linked to the side chains by means of a sulfonamide function (Scheme 4, Structure VI), was obtained by treating poly(L-lysine) with p-phenylazobenzenesulfonyl chloride. The poly(a-amino acid) was modified quantitatively conversion to the azo-lysine units of VI was effectively 100%. The azo-modified polypeptide was soluble in HFP, in which it exhibited an intense photochromism attributed to the trans-cis photoisomerization of the azobenzene units. Like other sulfonated azobenzene compounds, 33 azosulfonyl-modified polymers of L-lysine were found to be very stable in their tis form, and no thermal decay was observed at room temperature over periods of times as long as several weeks. Interconversion between the two forms at room temperature could only be effected by irradiation at appropriate wavelengths. This behavior allowed the authors to purify the trans and cis forms of the model compound NE-azobenzenesulfonyl-L-lysine (VII) by chromatography, and to measure the absorption spectra of the two pure photoisomers. 

The bifunctional pyrrolidine sulfonamide catalyst, 38, having basic pyrrolidine nitrogen and Bronsted acidic sulfonamide function, mediates the addition of aldehydes to nitrostyrenes in high yield and selectivity (Scheme 2.47) [34]. Alkyl-substituted nitroolefins afford, however, product in low yield and in low selectivity. 

Lately, Willis and coworkers [97,98] have developed a cascade N-annu-lation route to 1-functionalized indoles. Amine, aniline, amide, carbamate, and sulfonamide functional groups can efficiently be introduced as coupling partners if 2-(2-bromo-phenyl)-cyclohex-l-enyl triflate 112 is reacted in the presence of [Pd2dba3] and dpephos or xantphos as ligands to give a variety of tetrahydrocarbazoles 113 in moderate to excellent yields (Scheme 41). 

The Kenner sulfonamide-based SC linker 1.27 was supported on PS resin (84) allowing the attachment of carboxylic acids or amino acids to the sulfonamide function. After synthetic elaboration, treatment with diazomethane produces the A-methylacylsulfonamide, which can be cleaved with nucleophiles such as 0.5 N NHs-dioxane or hydrazine-MeOH, 0.5 N NaOH, releasing amides, hydrazides, or carboxylic acids, respectively. A modification using iodoacetonitrile produces the more labile A-cyanomethyl derivative, which can be cleaved completely with stoichiometric amounts of amines to release the corresponding amides into solution. 

Anelh, P.L., Bertini, 1., Fragai, M., et al. (2000) Sulfonamide-functionalized gadolinium DTPA complexes as possible contrast agents for MRI a relaxometric investigation. European Journal of Inorganic Chemistry, 625-630. 

The aromatic ring and the sulfonamide functional group are both required. 

Table 4.1 lists the methods that have been used to remove the tosyl groups. There are other methods to cleave the sulfonamide functions in linear compounds but they did not work on the macrocyclic sulfonamides (Muller, 1957). 

The sulfoxide and the sulfonamide functions are very polar and usually confer mediocre CNS bioavailability. However, sulfonamides presenting moderate brain penetration ( 10%) are known. An example is found with the S-HTs receptor antagonist SB-271046 (Fig. 19.42). 

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