Galactostatin, a new .BETA.-galactosidase inhibitor from Streptomyces lydicus.

Miyake, Yukio; Ebata, Mitsuo

doi:10.7164/antibiotics.40.122

Cited by 33 publications

(10 citation statements)

References 6 publications

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“…The amino-sugar analog migalastat (galactostatin) was isolated as a fermentation product and is close in structure to nojirimycin ( 13a ) and galactose ( 13b ) . Because miglustat ( 13c ) was similar to the terminal galactose of the substrate for α-galactoside A, globotriasoylceramide, the natural product has been considered as a possible modulator of the enzyme .…”

Section: Case Studies: Drugs From Biological and Clinical Efforts (Re...mentioning

confidence: 99%

Lead-like Drugs: A Perspective

Raymer

Bhattacharya

2018

J. Med. Chem.

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Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal chemistry practice. To examine the recent state-of-the-art in lead-like drug discovery, we surveyed recent drug approvals from 2011 to 2017 and top 200 prescribed medications, as well as provide case studies on recently approved lead-like drugs. Many of these recent drugs are close analogs of previously known drugs or natural substrates, with a key focus of their medicinal chemistry optimization being the choice of a low molecular weight starting point and maintaining low molecular weight during the optimization. However, the identification of low molecular weight starting points may be limited by the availability of suitable low molecular weight screening sets. To increase the discovery rate of lead-like drugs, we suggest an increased focus on inclusion and prosecution of lead-like starting points in screening libraries.

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Section: Case Studies: Drugs From Biological and Clinical Efforts (Re...mentioning

confidence: 99%

Lead-like Drugs: A Perspective

Raymer

Bhattacharya

2018

J. Med. Chem.

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“…This was given the trivial name of nojirimycin following structural characterisation after isolation from Streptomyces nojiriensis [37][38][39]. The finding of two related compounds nojirimycin B (2) and galactostatin (3) followed soon after [40,41]. The isolation and identifcation of iminosugars from plants proceeded these initial discoveries from micro-organisms, firstly with the monocyclic structures fagomine (4) and moranoline (5, deoxynojirimycin) followed by the isolation of bicyclic structures.…”

Section: Iminosugars: Classification Occurrence and Historical Contextmentioning

confidence: 99%

Iminosugars: Therapeutic Applications and Synthetic Considerations

Horne

2014

Topics in Medicinal Chemistry

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Iminosugars, carbohydrate mimetics in which the endocyclic oxygen of the parent carbohydrate is replaced with nitrogen, are the most important class of carbohydrate mimetic reported to date with two marketed drugs and several in clinical development. Since their first isolation in the 1960s iminosugars have captured the imagination of both synthetic and medicinal chemists alike with recent therapeutic developments highlighting the need for improved routes of synthesis. The resurgence in the therapeutic application of iminosugars has arisen as a consequence of our growing understanding on the role that glycobiology plays in disease and development. There are myriad possible individual targets encompassing a range of therapeutic areas, all of which can potentially be addressed by iminosugars. This chapter presents the historcial development of this compound class before discussing some of the issues that iminosugars present as synthetic targets. The therapeutic potential of this class of compound with specific reference to the development of modulators of glucocerebrosidase activity is discussed.

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“…1-Deoxygalactonojirimycin (galactostatin, 11) a known powerful competitive inhibitor of plant -galactosidase [58][59][60], was examined as a candidate of chemical chaperon in the treatment of Fabry's disease ( Fig. 5) [61].…”

Section: Inhibitors Of Galactosidasesmentioning

confidence: 99%

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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Galactostatin, a new .BETA.-galactosidase inhibitor from Streptomyces lydicus.

Cited by 33 publications

References 6 publications

Lead-like Drugs: A Perspective

Lead-like Drugs: A Perspective

Iminosugars: Therapeutic Applications and Synthetic Considerations

3,4-Dihydroxypyrrolidine as Glycosidase Inhibitor

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