Synthesis of heterocyclic N-(β-d-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase

Kónya, Bálint; Docsa, Tibor; Gergely, Pál; Somsák, László

doi:10.1016/j.carres.2012.01.020

Cited by 25 publications

(13 citation statements)

References 28 publications

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“…There have been several examples of arenes functionalized with 1,2,3‐triazoles at the meta position (Figure 1). 5a–e Herein, we present a simple protocol for the regioselective conversion of an aryl meta CH to the corresponding 1,2,3‐triazole by direct CH borylation followed by Cu II ‐catalyzed azidation of the aryl boronate. The azidation has been achieved by using just 1 mol % of Cu(OTf) 2 using air as the sole oxidant.…”

Section: Methodsmentioning

confidence: 99%

Regioselective Conversion of Arenes to N‐aryl‐1,2,3‐triazoles Using CH Borylation

Srinivasan

Coyne

Abell

2014

Chemistry A European J

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A one-pot protocol for the synthesis of N-aryl 1,2,3-triazoles from arenes by an iridium-catalyzed CH borylation/copper catalyzed azidation/click sequence is described. 1 mol % of Cu(OTf)2 was found to efficiently catalyze both the azidation and the click reaction. The applicability of this method is demonstrated by the late-stage chemoselective installation of 1,2,3-triazole moiety into unactivated molecules of pharmaceutical importance.

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Section: Methodsmentioning

confidence: 99%

Regioselective Conversion of Arenes to N‐aryl‐1,2,3‐triazoles Using CH Borylation

Srinivasan

Coyne

Abell

2014

Chemistry A European J

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“…In 2012, Konya et al synthesized new glucose derivatives for the inhibition of GP [ 29 ]. They have reported on the synthesis and enzymatic evaluation of a series O -peracetylated N -( β - d -glucopyranosyl)-carboxamides with isoxazole or 1,2,3-triazole rings.…”

Section: N -Glycosides As Antidiabetic Agentsmentioning

confidence: 99%

“… Synthesis of N -(β- d -glucopyranosyl)-1-substituted-1,2,3-triazole-4-carboxamides 37 and N -(β- d -glucopyranosyl)-3-substituted-isoxazole-5-carboxamides 39 [ 29 ] …”

Section: N -Glycosides As Antidiabetic Agentsmentioning

confidence: 99%

In the Search of Glycoside-Based Molecules as Antidiabetic Agents

et al. 2019

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This review is an effort to summarize recent developments in synthesis of O -glycosides and N -, C -glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the O -glycosides used in the treatment of diabetes are presented, followed by the N -glycosides and finally the C -glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing potential drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order. C -Glycosyl compounds mimicking O -glycosides structure, exhibit the best features in terms of pharmacodynamics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various C -glycosides. Also N -glycosides such as N -(β- d -glucopyranosyl)-amides, N -(β- d -glucopyranosyl)-ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidiabetic agents. In order to indicate which of the compounds presented in the given sections have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing figures and the results of the ranking were placed. In this way, the reader can learn about the structure of the compounds having the best antidiabetic activity. The compounds, whose synthesis was described in the article but did not appear on the figures presenting the structures of the most active inhibitors, did not show proper activity as inhibitors. Thus, the article also presents studies that have not yielded the desired results and show directions of research that should not be followed. In order to show the directions of the latest research, articles from 2018 to 2019 are described in a separate Sect. 5 . In Sect. 6 , biological mechanisms of action of the glycosides and patents of marketed drugs are described.

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“…Heterocyclic compounds that have been identified as GP inhibitors include: caffeine [7], flavopiridol [25] and purine derivatives [6](purine nucleoside site, also known as the 'inhibitor' site); indirubin [26] and phthalic acid derivatives [6](AMP site); pyridine derivatives [6] (Bay W1807) (AMP site); indole-carboxamide derivatives, 3,4dihydroquinolin-2-ones and 5-chloroindoles (another allosteric site at the enzyme dimer interface) [26][27][28][29]. Recent examples, which continue to demonstrate the importance of exploration of structural diversity using heterocylic moieties, include conjugates of Dglucose, 1,3,4-oxadiazole, and 1,2,3-triazole [30], 1-xylosyl-4-substituted 1,2,3-triazoles [31], C-Glucopyranosyl-1,2,4-triazoles [32], C5-alkynyl, 4,5-spirolactams [33], alkylfurano [2,3-d]pyrimidine glucopyranonucleosides [34], and heterocyclic N-(β-Dglucopyranosyl)carboxamides [35].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, screening and docking of small heterocycles as Glycogen Phosphorylase inhibitors

Schweiker¹,

Loughlin²,

Lohning³

et al. 2014

European Journal of Medicinal Chemistry

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A series of morpholine substituted amino acids (phenylalanine, leucine, lysine and glutamic acid) was synthesized. A fragment-based screening approach was then used to evaluate a series of small heterocycles, including morpholine, oxazoline, dihydro-1,3-oxazine, tetrahydro-1,3-oxazepine, thiazoline, tetrahydro-1,3-pyrimidine, tetrahydro-1,3-diazepine and hexahydro-1H-benzimidazole, as potential inhibitors of Glycogen Phosphorylase a. Thiazoline 7 displayed an improved potency (IC50 of 25 μM) and had good LE and LELP values, as compared to heterocycles 1, 5, 9-13 and 19 (IC50 values of 1.1 mM-23.9 mM). A docking study using the crystal structure of human liver Glycogen Phosphorylase, provided insight into the interactions of heterocycles 5, 7, 9-13 and 19 with Glycogen Phosphorylase.

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Synthesis of heterocyclic N-(β-d-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase

Cited by 25 publications

References 28 publications

Regioselective Conversion of Arenes to N‐aryl‐1,2,3‐triazoles Using CH Borylation

Regioselective Conversion of Arenes to N‐aryl‐1,2,3‐triazoles Using CH Borylation

In the Search of Glycoside-Based Molecules as Antidiabetic Agents

Synthesis, screening and docking of small heterocycles as Glycogen Phosphorylase inhibitors

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