Assessment of synthetic methods for the preparation of N-β-d-glucopyranosyl-N′-substituted ureas, -thioureas and related compounds

Somsák, László; Felföldi, Nóra; Kónya, Bálint; Hüse, Csaba; Telepó, Katalin; Bokor, Éva; Czifrák, Katalin

doi:10.1016/j.carres.2008.01.045

Cited by 25 publications

(16 citation statements)

References 25 publications

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“…The glycogen phosphorylase inhibitor KB228 ( N -(3,5-dimethyl-benzoyl)- N’ -(β-D-glucopyranosyl)urea 4 ) was prepared according to a previously published procedure [31] as shown in Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

Glycogen Phosphorylase Inhibitor N-(3,5-Dimethyl-Benzoyl)-N’-(β-D-Glucopyranosyl)Urea Improves Glucose Tolerance under Normoglycemic and Diabetic Conditions and Rearranges Hepatic Metabolism

et al. 2013

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Glycogen phosphorylase (GP) catalyzes the breakdown of glycogen and largely contributes to hepatic glucose production making GP inhibition an attractive target to modulate glucose levels in diabetes. Hereby we present the metabolic effects of a novel, potent, glucose-based GP inhibitor (KB228) tested in vitro and in vivo under normoglycemic and diabetic conditions. KB228 administration enhanced glucose sensitivity in chow-fed and obese, diabetic mice that was a result of higher hepatic glucose uptake. Besides improved glucose sensitivity, we have observed further unexpected metabolic rearrangements. KB228 administration increased oxygen consumption that was probably due to the overexpression of uncoupling protein-2 (UCP2) that was observed in animal and cellular models. Furthermore, KB228 treatment induced mammalian target of rapamycin complex 2 (mTORC2) in mice. Our data demonstrate that glucose based GP inhibitors are capable of reducing glucose levels in mice under normo and hyperglycemic conditions. Moreover, these GP inhibitors induce accommodation in addition to GP inhibition - such as enhanced mitochondrial oxidation and mTORC2 signaling – to cope with the glucose influx and increased glycogen deposition in the cells, however the molecular mechanism of accommodation is unexplored.

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Section: Resultsmentioning

confidence: 99%

Glycogen Phosphorylase Inhibitor N-(3,5-Dimethyl-Benzoyl)-N’-(β-D-Glucopyranosyl)Urea Improves Glucose Tolerance under Normoglycemic and Diabetic Conditions and Rearranges Hepatic Metabolism

et al. 2013

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“…[346] The preparation of N-(β-d-glucopyranosyl)-N -substituted thioureas were accomplished by reaction of β-d-glucopyranosylammonium carbamate with an isothiocyanate in dry pyridine at room temperature. [347] The biological activity of macromolecules containing the 1-(acyl)thiourea group has also been evaluated. Thus, derivatives of chitosan were synthesized and their structures were characterized by FTIR spectroscopy.…”

Section: Biological Aspectsmentioning

confidence: 99%

A review on the chemistry, coordination, structure and biological properties of 1-(acyl/aroyl)-3-(substituted) thioureas

Saeed

Flörke

Erben

2013

Journal of Sulfur Chemistry

198

123

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This review provides an overview of the chemistry, structure and potential applications of 1-(acyl/aroyl)-3-(mono-substituted) and 1-(acyl/aroyl)-3,3-(di-substituted) thioureas, with general formula R 1 C(O)N (1) HC(S)N (3) R 2 R 3 . In recent years, the title compounds have found extensive applications as ligands in coordination chemistry. The effect that nitrogen substituents exert on the intra-and intermolecular hydrogen-bonding interactions is discussed, including their role on the coordination properties displayed by these ligands. Novel applications of transition metal complexes bearing 1-(acyl/aroyl)-3-(mono-and di-substituted) thioureas are introduced. Biological aspects are also highlighted. As recently demonstrated, high-throughput screening assay and structure-activity analyses are feasible for this class of compounds. The chemical versatility of 1-(acyl)-3-(substituted) thiourea molecules and the derived metal complexes, together with the possibility of determining detailed structural properties, join biological applications in a promising interdisciplinary approach. The bibliography includes 382 references with emphasis on the literature appearing after 2007.

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“…Therefore, acylation of compound 5 (Pinter et al, 1995) by zinc chloride (ZnCl 2 ) catalyzed reaction of the corresponding acyl chlorides RCOCl (a-f) gave derivatives 6a-f, in acceptable-tomoderate yields (35-67 %). Although the Lewis acidic zinc chloride not only activates acid chlorides but also catalyze iminium ion formation (Paulsen and Pflufhaupt, 1980;Isbell and Frush, 1958) and, thereby, anomerization (Somsák et al, 2008a, b), in our case, the b-anomers 6af were solely obtained. Their 1 H NMR spectra showed Hz and J 4,5 C 9.4 Hz) arising from the trans-diaxial orientation of these consecutive protons, indicating the b-configuration of the sugar moiety and equatorially oriented acetyl groups.…”

Section: Resultsmentioning

confidence: 59%

“…In view of the above observations and as a continuation of our long-term interest in glucopyranosyl analogues as antitumor/antiviral agents and potent enzyme inhibitors (Parmenopoulou et al, 2014;Dimopoulou et al, 2013;Manta et al, 2012;Kantsadi et al, 2012), it was envisaged that compounds bearing a glucopyranosyl moiety linked with various aralkyl and aralkenyl groups (Somsák et al, 2008a, b) via the pharmacophore linkers NHCO and NHCONHCO would be endowed with pronounced antitumor activity. We hereby report the facile synthesis and biological properties of novel acetylated as well as fully deprotected N-acyl-b-D-glucopyranosylamines (3a-f, 4af) and ureas (6a-f, 7a-f), respectively.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel N-acyl-β-d-glucopyranosylamines and ureas as potential lead cytostatic agents

et al. 2016

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Novel classes of acetylated and fully deprotected N-acyl-b-D-glucopyranosylamines and ureas have been synthesized and biologically evaluated. Acylation of the per-O-acetylated b-D-glucopyranosylurea (5), easily prepared via its corresponding phosphinimine derivative, by zinc chloride catalyzed reaction of the corresponding acyl chlorides RCOCl (a-f) gave the protected N-acyl-b-Dglucopyranosylureas (6a-f), in acceptable-to-moderate yields. Subsequent deacetylation of analogues 6a-f under Zemplén conditions afforded the fully deprotected derivatives 7a,b,d,e,f, while the desired urea 7c was formed after treatment of 6c with dibutyltin oxide. All protected and unprotected compounds were examined for their cytotoxic activity in different L1210, CEM and HeLa tumor cell lines and were also evaluated against a broad panel of DMA and RNA viruses. Derivative 7c exhibited cytostatic activity against the three evaluated tumor cell lines (IC 50 9-24 lL) and might be the basis for the synthesis of structure-related derivatives with improved cytostatic potential. Only analogue 6f weakly but significantly inhibited the replication of parainfluenza-3 virus, Sindbis virus and Coxsackie virus B4 in cell cultures at concentrations of 45-58 lM.

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Assessment of synthetic methods for the preparation of N-β-d-glucopyranosyl-N′-substituted ureas, -thioureas and related compounds

Cited by 25 publications

References 25 publications

Glycogen Phosphorylase Inhibitor N-(3,5-Dimethyl-Benzoyl)-N’-(β-D-Glucopyranosyl)Urea Improves Glucose Tolerance under Normoglycemic and Diabetic Conditions and Rearranges Hepatic Metabolism

Glycogen Phosphorylase Inhibitor N-(3,5-Dimethyl-Benzoyl)-N’-(β-D-Glucopyranosyl)Urea Improves Glucose Tolerance under Normoglycemic and Diabetic Conditions and Rearranges Hepatic Metabolism

A review on the chemistry, coordination, structure and biological properties of 1-(acyl/aroyl)-3-(substituted) thioureas

Synthesis of novel N-acyl-β-d-glucopyranosylamines and ureas as potential lead cytostatic agents

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