Synthesis of 2-amino-5-benzoyl-4-(2-furyl)thiazoles as adenosine A(2A) receptor antagonists.
ABSTRACT The discovery and synthesis of a series of 2-amino-5-benzoyl-4-(2-furyl)thiazoles as adenosine A(2A) receptor antagonists from a small-molecule combinatorial library using a high-throughput radioligand-binding assay is described. Antagonists were further characterized in the A(2A) binding assay and an A(1) selectivity assay. Selected examples exhibited excellent affinity for A(2A) and good selectivity versus the A(1) receptor.
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ABSTRACT: This Review summarizes and updates the work on adenosine A(2A) receptor antagonists for Parkinson's disease from 2006 to the present. There have been numerous publications, patent applications, and press releases within this time frame that highlight new medicinal chemistry approaches to this attractive and promising target to treat Parkinson's disease. The Review is broken down by scaffold type and will discuss the efforts to optimize particular scaffolds for activity, pharmacokinetics, and other drug discovery parameters. The majority of approaches focus on preparing selective A(2A) antagonists, but a few approaches to dual A(2A)/A(1) antagonists will also be highlighted. The in vivo profiles of compounds will be highlighted and discussed to compare activities across different chemical series. A clinical report and update will be given on compounds that have entered clinical trials.ACS Chemical Neuroscience 10/2011; 2(10):555-67. · 3.87 Impact Factor
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ABSTRACT: A series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamide and furamide analogues were investigated in radioligand binding studies at adenosine receptor subtypes with an aim to obtain potent and selective adenosine receptor ligands. Benzamide and furamide linked to thiazole was found to be crucial for high adenosine receptor affinity. The most potent compound indentified in this study was 5d with low nanomolar affinity for all four adenosine receptor subtypes. Compounds 5a and 5g showed moderate selectivity for A2A adenosine receptors. Molecular docking versus all four human adenosine receptors combined with membrane molecular dynamics studies were performed to rationalise the peculiar selectivity profile of 5d antagonist.European journal of medicinal chemistry 03/2013; 63C:924-934. · 3.27 Impact Factor
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ABSTRACT: Introduction: In 2008, we published our review titled 'Therapeutic potential of A1 adenosine receptor ligands - a survey of recent patent literature' that reported the compounds active on A1 adenosine receptors (ARs) and the applications of A1 AR ligands patented in the period 2005 - 2008. Areas covered: This article is a discussion of the patents about the same subjects, issued in the period 2008 to present. It is organized similarly to the first one, with a section about new compounds, subdivided on the basis of their functional activity (agonists, antagonists and allosteric modulators) and a section regarding new therapeutic applications. Expert opinion: The main novelty is represented by the patenting of A1 AR ligands with dual selectivity which may show, in some conditions, better efficacy and fewer side effects. Moreover, while the way to arrive into the market appears full of obstacles for selective A1 ligands that need systemic administration for long-term therapy, better chances are foreseen in applications requiring topical administration.Expert Opinion on Therapeutic Patents 05/2013; · 3.53 Impact Factor