ChemInform Abstract: Synthesis of Influenza Neuraminidase Inhibitors.

Abdel‐Magid, Ahmed F.; Maryanoff, Cynthia A.; Mehrman, Steven J.

doi:10.1002/chin.200225241

Cited by 12 publications

(15 citation statements)

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“…Synthesis of Methyl 5-(3-azidopropoxy)-2-hydroxybenzoate (2). To a solution of compound 4 (795 mg, 2.75 mmol) in anhydrous acetonitrile (30 mL) was added sodium azide (1.07 g, 16.50 mmol) and this mixture was stirred at reflux for 3 hours.…”

Section: Methodsmentioning

confidence: 99%

“…1 For example, the two drugs namely, zanamivir and oseltamivir, approved to date in combating both influenza A and B were derived from a pyranoglycosyl scaffold via computational study. 2 Indeed, the carbohydrate structure that contains multiple stereo-centers and reactive hydroxyl groups may favorably allow modification toward the construction of numerous structurally diverse glycomimetics. For instance, a 1-methoxy-O-glucoside has a primary hydroxyl group on C6 and three secondary hydroxyl groups respectively on C2, C3 and C4 with different reactivities and spatial orientations on its side chain, shown in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

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Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Tang¹,

Hu²,

He³

et al. 2011

Bulletin of the Korean Chemical Society

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The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6-and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged IC 50 value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Tang¹,

Hu²,

He³

et al. 2011

Bulletin of the Korean Chemical Society

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“…Inhibitors of angiotensin-converting enzyme (ACE) such as benazepril and enalapril offer much-reviewed examples [69,70]. Here, we focus on two neuraminidase inhibitors of value against type A and B influenza in humans [71][72][73]. Target-oriented rational design led to highly hydrophilic agents that are not absorbed orally.…”

Section: Oseltamivir a Prodrug For Oral Absorptionmentioning

confidence: 99%

Role of PhaseIMetabolism in Drug Activation and Clinical Treatment Outcomes

Testa

Pannatier

2012

Encyclopedia of Drug Metabolism and Interactions

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This chapter explores the relation between drug biotransformation and pharmacological activity. More precisely, it surveys the formation of active metabolites and exemplifies cases of metabolites as or more active than the parent drug. Because very few drug conjugates are pharmacologically active, the focus is on metabolic reactions of functionalization (i.e., phase I), namely, oxidations, reductions, or hydrolyses.The first section sets the scene by explaining the pharmacokinetic/pharmacodynamic (PK/PD) interplay that underlies drug action, and the existing continuum ranging from drugs devoid of active metabolites, to drugs yielding some active metabolite(s), to prodrugs whose activity is due solely to the metabolite. Soft drugs are briefly exemplified since they nicely illustrate the concept of drugs designed to be rapidly metabolized to inactive, atoxic metabolites.

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“…33 The avian infl uenza H5N1 virus may cause severe lower respiratory tract (LRT) disease in humans because it attaches predominantly to type II pneumocytes, alveolar macrophages, and nonciliated bronchiolar cells of the human LRT. 34 In terms of the effectiveness of neuraminidase inhibitors, it would not, in theory, matter whether NANA is bound via an α -2,3 or α -2,6 linkage, because the neuraminidase inhibitors act as transition state analogues 35 of NANA, irrespective on how it is bound to the penultimate galactose unit.…”

Section: Neuraminidase Inhibitors: Zanamivir and Oseltamivirmentioning

confidence: 99%

Existing Influenza Antivirals: Their Mechanisms of Action and Potential in the Face of Avian Influenza

Clercq

2007

Combating the Threat of Pandemic Influenza

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ChemInform Abstract: Synthesis of Influenza Neuraminidase Inhibitors.

Cited by 12 publications

References 0 publications

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Role of PhaseIMetabolism in Drug Activation and Clinical Treatment Outcomes

Existing Influenza Antivirals: Their Mechanisms of Action and Potential in the Face of Avian Influenza

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