Aryl sulfonamide

Sulfonylureas are not directly amenable to gas chromatography (GC) because of their extremely low volatility and thermal instability. GC has been used in conjunction with diazomethane derivatization, pentafluorobenzyl bromide derivatization, and hydrolysis followed by analysis of the aryl sulfonamides. These approaches have not become widely accepted, owing to poor performance for the entire family of sulfonylureas. Capillary electrophoresis (CE) has been evaluated for water analysis and soil analysis. The low injection volumes required in CE may not yield the required sensitivity for certain applications. Enzyme immunoassay has been reported for chlorsulfuron and triasulfuron, with a limit of detection (LOD) ranging from 20 to 100 ng kg (ppt) in soil and water. 

Amides and sulfonamides undergo intramolecular chemistry to form aryl amides and aryl sulfonamides (Equations (17)—(19)) in the presence of palladium catalysts ligated by arylphos-phines.35,89 Initially, complexes of P(furyl)3 and P(o-tol)3 were most effective catalysts, but complexes of Hayashi s MOP and van Leeuwen s DPEphos and xantphos have lately been shown to be more active.90 In the presence of catalysts containing one of these ligand systems, five-, six-, and seven-membered rings were formed from halogenated benzamides or from substrates containing an acetamide, an A-carbobenzyloxy, or a t-butylcarbamate substituent tethered to the aryl halide (Equations (18) and (19)) ... 

Several patents claiming aryl sulfonamides have recently appeared [117-121], In the first, compound 43 was described to be effective in the rat collagen-induced arthritis model when dosed at 100 mpk (s.c., q.d., from day 9-17) [117]. This patent also reported that compound 44 significantly inhibited the number of monocytes recruited following thioglycolate injection in a rat peritonitis model. Two other patent applications describe sulfonamides 45 [120] and 46 [121] as CCR2 antagonists. 

This procedure is satisfactory for the synthesis of a variety of aryl sulfonamides. The heterocyclic intermediate used in the synthesis of chlorsulfuron is prepared according to K. R. Hoffmann and F. C. Schaeffer (Ref. 5) as shown in Figure 5. 

Nagao has disclosed bifunctional chiral sulfonamide 69 as being effective for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at room temperature in ether [228], Catalyst 69 is a 1,2-diamine derivative in which one of the nitrogens presents as an acidic NH group (part of an electron deficient aryl sulfonamide) and the other as a nucleophihc/basic teri-amine group with the intention to act synergistically in activation of the substrate carbonyl function and thiol nucleophile respectively (Fig. 16) [228],... 

The Eu(III) and Tb(III) complexes of 36, developed by Parker et al., showed modulation of the lanthanide emission caused by changes in pH [139]. The coordinating antenna was covalently attached to the complex but only coordinates to the metal centre under specific pH conditions. This was demonstrated on a cyclen complex where three carboxylate pendant arms were attached, allowing coordination to take place, and resulted in the formation of a charge-neutral complex. The fourth position contained an aromatic sulfonamide tethered via an ethyl carbon chain, 36a-36c. Studies showed that luminescence was switched on when the complexes were in alkaline conditions because the two metal-bound waters (q = 2) were displaced. This led to a situation where the pendant aryl sulfonamide groups were coordinated... 

Fused 1,2-thiazetidine A-oxides 22 are produced in one step from readily available aryl sulfonamides by cycloaddition with quadricyclane (Equation 13) <1997SL167, 1997SL634>. 

The use of click chemistry has also been applied to the synthesis of benzophe-none-modified y-secretase probes. The group of Yao reported the preparation of a compound library built up from Bpa-containing alkyne 77 and azide 78 (Fig. 7) [81]. The azide part contains a racemic hydroxyethylene moiety, and variations were made in its aryl sulfonamide domain. The compound library was screened for its potency against y-secretase inhibition and the most potent compounds were used to label active PS1 in a cell lysate. In addition, Fuwa and coworkers reported a divergent synthesis of y-secretase A/BPs by means of click chemistry with alkyne 79 and azide 80 [82]. Variations were made in the aryl part of the alkyne (dibenzoazepine or benzodiazepine) and in the type of spacer between the benzo-phenone moiety and biotin in the azide. PAL using these probes provided the authors with evidence that the molecular target of this type of probe is the N-terminal fragment of PS1. 

Garigipati and Adams [61] reported a chemical encoding procedure, based on novel photochemically cleavable aryl sulfonamides as inert tags with a robust and reliable chemistry. An example of a 1000-member encoded library was provided without experimental details, so additional applications of these chemical tags need to be disclosed in order to have a better understanding of their strengths and limitations. 

N-Aryl sulfonamides have not been investigated in detail, but anion translocation from the -substituted ring to the Af-substituted ring takes place in diaryl sulfonamides 255, ultimately leading to a rearrangement as shown below.219 220... 

The chloramine derivatives (ArS02NClNa) of a variety of other aryl-sulfonamides (Ar = phenyl, o-tolyl, p-chlorophenyl,/>-nitrophenyl, and o-carboalkoxyphenyl) have been used successfully in these catalytic oxy-aminations. Since only chloramine-T (Ar = p-tolyl) and chloramine-B (Ar = phenyl) are commercially available, we have developed a convenient procedure for generating the chloramines in situ for use in the modification involving phase-transfer catalysis. One simply stirs a suspension of the arylsulfonamide with an equivalent of sodium hypochlorite (Clorox) until a homogeneous solution is obtained. When this solution is used in the PTC method (see Ref. 2 for experimental details), the yields of oxyaminated product are comparable with those obtained with isolated chloramine salts. 

Reaction of epichlorohydrine with aryl sulfonamides afforded a mixture of the cyclodimerization products, as and trans l,5-bis(arylsulfonyl)-3,7-dihydroxyoctahydro-l,5-diazocines 90a,c <1995JOC1959, 1998JOC1566, 2006LJSP7145003>. 

A key step in this direction involved the synthesis of analogues having an aryl-sulfonamide as replacement for one of the Cbz-L-leucine groups as seen in ke-... 

Figure 4 Structures of small molecule inhibitors of (a, b) CDK, (c) HSP90, (d) survivin gene expression, (e-l) XIAP, and (m) omi/HtrA2. (a) flavopiridol, (b) purvalanol, (c) 5-aminoimidazole-4-carboxamide-1 -beta-D-ribofuranoside (AlCAR), (d) YM155, (e-h) SMAC-mimetics, (i) Smac mimetic tetrazoyl thioether, (j) benzoquinone embelin, (k) aryl sulfonamide, (I) XIAP inhibitor of Polyphenylurea series, (m) Omi/HtrA2 inhibitor Ucf-101.

The number of chiral diazaaluminolidine catalysts has been extended by Dymock, Kocienski and Pons, who introduced the more convenient to handle trimethylsilyl-ketene [31]. The catalysts in this study were prepared from slightly different sulfonamides but asymmetric induction was comparable with that obtained with the ketene and similar aldehydes. With trimethylsilylketene, two diastereomers are possible and in all examples studied the cis isomer 126 was the predominate product. TTie reactions in Table 7 were performed with 30 mol % catalyst—with 20 mol % catalyst the reaction is incomplete. A more active catalyst can be prepared from the bis-trifluoro-methylsulfonyl derivative of 128, but asymmetric induction was low. It was reported that ortho substituents on the aryl sulfonamide were necessary for higher induction but data were provided only for the aryl sulfonamide substituents summarized in Table 7. Both symmetrical and unsymmetrical diazaaluminolidines were examined as catalysts in an attempt to optimize asymmetric induction but significant differences were not found. The catalyst prepared from the symmetric bis-sulfonamide 128 with Ar = 2,4,6-tri-/yo-propylphenyl did not give any reaction even at 100 mol %. 

There are no examples in the literature of light-induced deprotection of the guanidine moiety of arginine. The tosyl group and other aryl sulfonamides are conunonly used. It is conceivable that the photochemical donor-acceptor protocol developed by Hamada et al.l vide supra) could be utilized to affect photodeprotection of arginine arylsulfonamides. 

Besides their good electrochemical stability, most of the tested polymers present an identical behavior toward usual chemical reagents as well as a functionalization similar to the classical polystyrene beads. All supported molecules formed by successive chemical steps were cleaved off from the conducting resin by the cathodic S—N bond scission of the aryl sulfonamide moiety. 

In order to choose the best carboxyhc acid bioisoster pXa and log P are important parameters to look at before proceeding with one surrogate or another. An interesting study comparing p Ta and log P values of some aryl phosphonic acids, aryl tetrazoles, and aryl sulfonamides has been published by Franz. The values of pA and log P are very important parameters in drug design. Several pubhshed examples show that the interchange of carboxylic acid for tetrazole and... 

Another inhibitor series has been used to estimate the value of P pocket interactions - the Boehringer Mannheim di aryl sulfonamides [39] (also reported by 3-Di-mensional Pharmaceuticals [40-43]) (Fig. 7.11). 

Dahl R, Sergienko EA, Su Y et al (2009) Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). J Med Chem 52 6919-6925... 

Aryl sulfonamides were targeted as potential anti-MRS pharmacophores of... 

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