New leads for selective inhibitors of α-l-fucosidases. Synthesis and glycosidase inhibitory activities of [(2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl]furan derivatives

Robina, Inmaculada; Vargas, Ângelo; Fernández-Bolaños, José G.; Fuentes, José; Demange, Raynald; Vogel, Pierre

doi:10.1016/s0960-894x(01)00497-8

Cited by 42 publications

(12 citation statements)

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“…In recent years, we have been actively working on the development of new iminocyclitols with inhibitory activity towards α-fucosidases. [6][7][8][9] We have shown that the presence of an additional aromatic or heteroaromatic binding component close to the five membered iminocyclitol increases notably their inhibitory activity (1 10 vs. 2, 8 Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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Rapid discovery of potent α-fucosidase inhibitors by in situ screening of a library of (pyrrolidin-2-yl)triazoles

et al. 2014

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The synthesis of a small library of (pyrrolidin-2-yl)triazoles via copper catalysed cycloaddition of an alkynyl iminocyclopentitol and a set of commercial and synthetic azides has been achieved. The in situ screening for the activity towards α-fucosidase of the resulting triazoles has allowed the identification of one of the most potent and selective pyrrolidine derived inhibitors of this enzyme (Ki = 4 nM).

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Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] We have shown that the presence of an additional aromatic or heteroaromatic binding component close to the five membered iminocyclitol increases notably their inhibitory activity (1 10 vs. 2, 8 Fig. 1).…”

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confidence: 99%

Rapid discovery of potent α-fucosidase inhibitors by in situ screening of a library of (pyrrolidin-2-yl)triazoles

et al. 2014

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“…6 We have also found that [(2S,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]furan derivatives 5 are good b-galactosidase inhibitors whereas their C-2 epimers 6 are good and selective a-L-fucosidase inhibitors. 9 a-L-Fucosidases participate in the last stages of glycoprotein biosynthesis and their inhibitors have been found to inhibit the cytophatic effect of HIV and reduce infection. 4 a-L-Fucosidases also facilitate sperm transport and sperm-egg interactions.…”

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confidence: 99%

Stereoselective synthesis of (2S,3S,4R,5S)-5-methylpyrrolidine-3,4-diol derivatives that are highly selective α-l-fucosidase inhibitors

et al. 2005

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“…The inhibitory activity of 64 towardsgalactosidase and -mannosidase is quite similar to that of A powerful inhibitior 85 against -fucosidase is similar to that of compound 63 [77,104]. Compounds with (2R,3R,4S)-configuration (86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97) showed moderate inhibitory activities against -mannosidase [89], and those with a (2R,3S,4R)-configuration (98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109) tend to inhibitglucosidase and -galactosidase [88,89,93,109,110]. The specificity of these compounds was explained based on the similarity with substrate structures of individual enzymes where it was considered that a flexible pyrrolidine structure could adopt a 4 E conformation and 2-and 3-OH groups might mimic the hydroxyl groups of glucopyranosyl cation species (Fig.…”

Section: Cis-diol (B-type) [64777899102-108]mentioning

confidence: 68%

3,4-Dihydroxypyrrolidine as Glycosidase Inhibitor

Suzuki

Nakahara²,

Kanie³

2009

CTMC

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Glycosidases are involved in various important biological processes including digestion of starch in the intestine, oligosaccharide processing inside rough ER and Golgi apparatus, and degradation of glycoconjugates in lysosomes. It is apparent that inhibitors of this class of enzymes are useful in the investigation of biological functions of glycoconjugates. Furthermore, it is believed that these compounds are important as pharmaceuticals. The structures of glycosidase inhibitors can be categorized into two major classes; ground-state mimetics and transition-state mimetics. The former has a chair-shaped six-membered structure that mimics monosaccharides where ring oxygens are often replaced with other elements for an improved binding affinity. On the other hand, the latter possesses a somewhat distorted shape compared with the chair conformation of carbohydrates. One of the ways to derive such distortion is by the introduction of sp2 character into the six-membered ring, and another is by ring contraction to form a five-membered system for the transition-state mimetics. The functions of these transition-state mimetics are often unpredictable regarding inhibitory activity and enzyme specificity. This review focuses on such "difficult to predict" species in an attempt to extract information or common aspects for the future development of inhibitors of glycosidases based on transition-state mimetics.

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New leads for selective inhibitors of α-l-fucosidases. Synthesis and glycosidase inhibitory activities of [(2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl]furan derivatives

Cited by 42 publications

References 45 publications

Rapid discovery of potent α-fucosidase inhibitors by in situ screening of a library of (pyrrolidin-2-yl)triazoles

Rapid discovery of potent α-fucosidase inhibitors by in situ screening of a library of (pyrrolidin-2-yl)triazoles

Stereoselective synthesis of (2S,3S,4R,5S)-5-methylpyrrolidine-3,4-diol derivatives that are highly selective α-l-fucosidase inhibitors

3,4-Dihydroxypyrrolidine as Glycosidase Inhibitor

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