ArticleJournal of medicinal chemistry1997
Structure-activity relationships of 4-(phenylethynyl)-6-phenyl-1,4-dihydropyridines as highly selective A3 adenosine receptor antagonists.
Article in Journal of medicinal chemistry, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 76 citations in OpenAlex.
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- Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development.Molecular diversity · 2022Review
- AMedicinal research reviews · 2018Review
- Computational studies to predict or explain G protein coupled receptor polypharmacology.Trends in pharmacological sciences · 2014Article
- Adenosine A(1) and prostaglandin E receptor 3 receptors mediate global airway contraction after local epithelial injury.American journal of respiratory cell and molecular biology · 2013Article
- Structure-activity relationships of 1,4-dihydropyridines that act as enhancers of the vanilloid receptor 1 (TRPV1).Bioorganic & medicinal chemistry · 2008Article
- Reperfusion injury: does it exist?Journal of molecular and cellular cardiology · 2007Review
- Progress in the pursuit of therapeutic adenosine receptor antagonists.Medicinal research reviews · 2006Review
- Techniques: Recent developments in computer-aided engineering of GPCR ligands using the human adenosine A3 receptor as an example.Trends in pharmacological sciences · 2005Review
- Synthesis and antitumor activity of 5-trifluoromethyl-2,4- dihydropyrazol-3-one nucleosides.Molecules (Basel, Switzerland) · 2004Article
- Structure-activity relationships of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists.Bioorganic & medicinal chemistry · 2004Article
- 1,4-Dihydropyridines as calcium channel ligands and privileged structures.Cellular and molecular neurobiology · 2003Review
- 9-Ethyladenine derivatives as adenosine receptor antagonists: 2- and 8-substitution results in distinct selectivities.Naunyn-Schmiedeberg's archives of pharmacology · 2003Article
- 2-Phenylimidazo[2,1-i]purin-5-ones: structure-activity relationships and characterization of potent and selective inverse agonists at Human A3 adenosine receptors.Bioorganic & medicinal chemistry · 2003Article
- Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells.Biochemical pharmacology · 2003Article
- In search of selective P2 receptor ligands: interaction of dihydropyridine derivatives at recombinant rat P2X(2) receptors.Journal of the autonomic nervous system · 2000Article
- Pyran Template Approach to the Design of Novel ADrug development research · 1999Article
- Selective A(3) adenosine receptor antagonists: water-soluble 3, 5-diacyl-1,2,4-trialkylpyridinium salts and their oxidative generation from dihydropyridine precursors.Journal of medicinal chemistry · 1999Article
- Chiral resolution and stereospecificity of 6-phenyl-4-phenylethynyl- 1,4-dihydropyridines as selective A(3) adenosine receptor antagonists.Journal of medicinal chemistry · 1999Article
- Synthesis, CoMFA analysis, and receptor docking of 3,5-diacyl-2, 4-dialkylpyridine derivatives as selective A3 adenosine receptor antagonists.Journal of medicinal chemistry · 1999Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
4-(Phenylethynyl)-6-phenyl-1,4-dihydropyridine derivatives are selective antagonists at human A3 adenosine receptors, with Ki values in a radioligand binding assay vs [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine) in the submicromolar range. In this study, structure-activity relationships at various positions of the dihydropyridine ring (the 3- and 5-acyl substituents, the 4-aryl substituent, and 1-methyl group) were probed synthetically. Using the combined protection of the 1-ethoxymethyl and the 5-[2-(trimethylsilyl)ethyl] ester groups, a free carboxylic acid was formed at the 5-position allowing various substitutions. Selectivity of the new analogues for cloned human A3 adenosine receptors was determined vs radioligand binding at rat brain A1 and A2A receptors. Structure-activity analysis at adenosine receptors indicated that pyridyl, furyl, benzofuryl, and thienyl groups at the 4-position resulted in, at most, only moderate selectivity for A3 adenosine receptors. Ring substitution (e.g., 4-nitro) of the 4-phenylethylnyl group did not provide enhanced selectivity, as it did for the 4-styryl-substituted dihydropyridines. At the 3-position of the dihydropyridine ring, esters were much more selective for A3 receptors than closely related thioester, amide, and ketone derivatives. A cyclic 3-keto derivative was 5-fold more potent at A3 receptors than a related open-ring analogue. At the 5-position, a homologous series of phenylalkyl esters and a series of substituted benzyl esters were prepared and tested. (Trifluoromethyl)-, nitro-, and other benzyl esters substituted with electron-withdrawing groups were specific for A3 receptors with nanomolar Ki values and selectivity as high as 37000-fold. A functionalized congener bearing an [(aminoethyl)amino]carbonyl group was also prepared as an intermediate in the synthesis of biologically active conjugates.
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