Sulfamate sweeteners

Spillane, William J.; Ryder, Caroline A.; Walsh, Maria R.; Curran, Patrick J.; Concagh, Danny G.; Wall, Siobhan N.

doi:10.1016/0308-8146(96)00022-2

Cited by 35 publications

(17 citation statements)

References 13 publications

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“…The Osubstituted derivatives 2 possess inhibitory activity against several types of unrelated enzymes, such as the CAs and the steroid sulfatases (STSs, EC 3.1.6.2) among others, [2][3][4][5][6][8][9][10] whereas the N-substituted compounds 3 primarily show applications as sweeteners. 11 The di/trisubstituted sulfamates 4 and 5 on the other hand show a very large variety of biological activities, as it will be presented in the review. The present paper will deal mainly with derivatives of types 2, 4, and 5, since the sulfamate sweeteners have thoroughly been reviewed earlier.…”

Section: Introductionmentioning

confidence: 99%

“…The present paper will deal mainly with derivatives of types 2, 4, and 5, since the sulfamate sweeteners have thoroughly been reviewed earlier. 11 The surprising pharmacological and medicinal chemistry applications of these compounds will be reviewed considering the specific targets with which they interact. To our best knowledge, this review broadens the area by being the first comprehensive one for this class of derivatives considering all their biological activity and possible pharmacological applications.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sulfamates and their therapeutic potential

Winum¹,

Scozzafava²,

Montéro³

et al. 2004

Medicinal Research Reviews

196

153

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Starting from the very simple molecule sulfamic acid, O-substituted-, N-substituted-, or di-/tri-substituted sulfamates may be obtained, which show specific biological activities which were or started to be exploited for the design of many types of therapeutic agents. Among them, sulfamate inhibitors of aminoacyl-tRNA synthetases (aaRSs) were recently reported, constituting completely new classes of antibiotics, useful in the fight of drug-resistant infections. Anti-viral agents incorporating sulfamate moieties have also been obtained, with at least two types of such derivatives investigated: the nucleoside/nucleotide human immunodeficiency virus (HIV) reverse transcriptase inhibitors, and the HIV protease inhibitors (PIs). In the increasing armamentarium of anti-cancer drugs, the sulfamates occupy a special position, with at least two important targets evidenced so far: the steroid sulfatases (STSs) and the carbonic anhydrases (CAs). An impressing number of inhibitors of STSs of the sulfamate type have been reported in the last years, with several compounds, such as 667COUMATE among others, progressing to clinical trials for the treatment of hormone-dependent tumors (breast and prostate cancers). This field is rapidly evolving, with many types of new inhibitors being constantly reported and designed in such a way as to increase their anti-tumor properties, and decrease undesired features (for example, estrogenicity, a problem encountered with the first generation such inhibitors, such as EMATE). Among the many isozymes of CAs, at least two, CA IX and CA XII, are highly overexpressed in tumors, being generally absent in the normal tissues. Inhibition of tumor-associated CAs was hypothesized to lead to novel therapeutic approaches for the treatment of cancer. Many sulfamates act as very potent (low nanomolar) CA inhibitors. The X-ray crystal structure of the best-studied isozyme, CA II, with three sulfamates (sulfamic acid, topiramate, and EMATE) has recently been reported, which allowed for a rationale drug design of new inhibitors. Indeed, low nanomolar CA IX inhibitors of the sulfamate type have been reported, although such compounds also act as efficient inhibitors of isozymes CA I and II, which are not associated with tumors. A large number of anti-convulsant sulfamates have been described, with one such compound, topiramate, being widely used clinically as anti-epileptic drug. By taking into consideration a side effect of topiramate, an anti-epileptic drug leading to weight loss in some patients, it has recently been proposed to use this drug and related sulfamates for the treatment of obesity. The rationale of this use is based on the inhibition of the mitochondrial CA isozyme, CA V, involved in lipogenesis. Some sulfamates were also shown to possess potent inhibitory activity against acyl coenzyme A:cholesterol acyltransferase, an enzyme involved in cholesterol metabolism. One such agent, avasimibe, is in advanced clinical trials for the treatment of hyperlipidemia and atherosclerosis. Thus, the sulfamate ...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sulfamates and their therapeutic potential

Winum¹,

Scozzafava²,

Montéro³

et al. 2004

Medicinal Research Reviews

196

153

View full text Add to dashboard Cite

show abstract

“…They are widely used in the production of pharmaceuticals and sweeteners. [1][2][3] Among the sulfamates, synthesis and investigation of biological activates of the N-monoalkylated sulfamates are absent in the literature, perhaps because their selective synthesis is challenging, due to competitive N-di-alkylation. The existing method for the preparation of N-monoalkylated sulfamates generally involves the reaction of primary amines with chlorosulfates (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

The first general protocol forN-monoalkylation of sulfamate esters: benign synthesis ofN-alkyl Topiramate (anticonvulsant drug) derivatives

Saeidian

Abdoli

2015

Journal of Sulfur Chemistry

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A novel protocol for the highly selective N-monoalkylation of the sulfamate ester moiety has been developed. This reaction proceeded efficiently using alkyl halides, benzyl halides and α-halo ketones as the electrophile in the presence of KF-Al 2 O 3 as a cost-effective and robust catalyst. This approach provides new access to N-monoalkylated Topiramate (anticonvulsant drug) derivatives which are potentially of great importance in medicinal chemistry. O O O O O OSO 2 NH 2 O O O O O OSO 2 NR 2 O O O O O OSO 2 NHR RX, KF-Al 2 O 3 acetonitrile, 80ºC Topiramate N-monoalkyl Topiramate (major) N,N'-dialkyl Topiramate (minor) +

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“…Sulfamate derivatives have been known for several years as artifi cial sweeteners (cyclamates) [1], but therapeutic applications are numerous and have signifi cantly broadened in recent years [2,3]. They were fi rst known as anticonvulsants and the drug topimarate, discovered in 1980, is still used in clinical settings for the treatment of refractory epilepsy [4].…”

Section: Introductionmentioning

confidence: 99%

A Sequential Dual Cleavage of the Arylsulfamate Linker to Provide Both Sulfamate and Phenol Derivatives

Fournier¹,

Ciobanu²,

Poirier³

2015

ChemJMold

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Abstract. Tyramine sulfamate was linked to the trityl chloride resin and this polymeric solid support used to introduce two levels of molecular diversity by formation of peptide bonds. A dual cleavage strategy next generated in a sequential way (without resin split) two different types of compounds (phenol and arylsulfamate derivatives), which are therapeutically attractive types of compounds. Here, we used tyramine as a general scaffold, but other arylsulfamate derivatives could be judiciously used to extend the nature of synthesized compounds.

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Sulfamate sweeteners

Cited by 35 publications

References 13 publications

Sulfamates and their therapeutic potential

Sulfamates and their therapeutic potential

The first general protocol forN-monoalkylation of sulfamate esters: benign synthesis ofN-alkyl Topiramate (anticonvulsant drug) derivatives

A Sequential Dual Cleavage of the Arylsulfamate Linker to Provide Both Sulfamate and Phenol Derivatives

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