2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolone core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.
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Recent highlights in the synthesis and biological significance of pyrazole derivatives.
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Department of Chemistry, Faculty of Sciences, Al al-Bayt University, P. O. Box 130040, Mafraq, 25113, Jordan.
Article Synopsis
- Aza-heterocyclic scaffolds, such as pyrazoles, are important in pharmaceuticals and other industries due to their diverse applications and therapeutic potential.
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Isothiourea-Catalysed Acylative Kinetic Resolution of Tertiary Pyrazolone Alcohols.
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EaStCHEM, School of Chemistry, University of St Andrews, St Andrews, Fife, KY16 9ST, UK.
The development of methods for the selective acylative kinetic resolution (KR) of tertiary alcohols is a recognised synthetic challenge with relatively few successful substrate classes reported to date. In this manuscript, a highly enantioselective isothiourea-catalysed acylative KR of tertiary pyrazolone alcohols is reported. The scope and limitations of this methodology have been developed, with high selectivity observed across a broad range of substrate derivatives incorporating varying substitution at N(2)-, C(4)- and C(5)-, as well as bicyclic constraints within the pyrazolone scaffold (30 examples, selectivity factors (s) typically >100) at generally low catalyst loadings (1 mol %).
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View Article and Find Full Text PDFIntermolecular Aminocarbonylation of Alkenes using Concerted Cycloadditions of Iminoisocyanates.
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The aminocarbonylation of alkenes is a powerful method for accessing the β-amino carbonyl motif that remains underdeveloped. Herein, the development of intermolecular aminocarbonylation reactivity of iminoisocyanates with alkenes is presented. This includes the discovery of a fluorenone-derived reagent, which was effective for many alkene classes and facilitated derivatization.
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