ArticleJournal of medicinal chemistry1998
Derivatives of the triazoloquinazoline adenosine antagonist (CGS 15943) having high potency at the human A2B and A3 receptor subtypes.
Article in Journal of medicinal chemistry, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 92 citations in OpenAlex.
- Review
- Fluorescent APurinergic signalling · 2023Article
- ACurrent medicinal chemistry · 2022Review
- Directed Search of Anti-inflammatory Agents Among (3HQuinazoline- 4-ylidene)hydrazides of N-protected Amino acids and their Heterocyclization Products.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Article
- AMedicinal research reviews · 2018Review
- Break Down in Order To Build Up: Decomposing Small Molecules for Fragment-Based Drug Design with eMolFrag.Journal of chemical information and modeling · 2017Article
- Functional selectivity of adenosine A1 receptor ligands?Purinergic signalling · 2013Article
- Cytotoxicity and anti-inflammatory activity of methylsulfanyl-triazoloquinazolines.Molecules (Basel, Switzerland) · 2013Article
- 2-Benz-yloxy-1,2,4-triazolo[1,5-a]quinazolin-5(4H)-one.Acta crystallographica. Section E, Structure reports online · 2011Article
- Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: A complete structure-activity profile.Purinergic signalling · 2007Article
- Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor.Journal of molecular graphics & modelling · 2006Article
- Progress in the pursuit of therapeutic adenosine receptor antagonists.Medicinal research reviews · 2006Review
- CGH2466, a combined adenosine receptor antagonist, p38 mitogen-activated protein kinase and phosphodiesterase type 4 inhibitor with potent in vitro and in vivo anti-inflammatory activities.British journal of pharmacology · 2005Article
- The receptor mechanism mediating the contractile response to adenosine on lung parenchymal strips from actively sensitised, allergen-challenged Brown Norway rats.Naunyn-Schmiedeberg's archives of pharmacology · 2005Article
- Structure-activity relationships of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists.Bioorganic & medicinal chemistry · 2004Article
- Demystifying the three dimensional structure of G protein-coupled receptors (GPCRs) with the aid of molecular modeling.Chemical communications (Cambridge, England) · 2003Review
- 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
- Evidence for an atypical receptor mediating the augmented bronchoconstrictor response to adenosine induced by allergen challenge in actively sensitized Brown Norway rats.British journal of pharmacology · 2002Article
- Potent P2XDrug development research · 2001Article
- [3H]MRS 1754, a selective antagonist radioligand for A(2B) adenosine receptors.Biochemical pharmacology · 2001Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1, 5-c]quinazolin-5-amine (CGS 15943) binds nonselectively to human A1, A2A, and A3 receptors with high affinity. Acylated derivatives and one alkyl derivative of the 5-amino group and other modifications were prepared in an effort to enhance A2B or A3 subtype potency. In general, distal modifications of the N5-substituent were highly modulatory to potency and selectivity at adenosine receptors, as determined in radioligand binding assays at rat brain A1 and A2A receptors and at recombinant human A3 receptors. In Chinese hamster ovary cells stably transfected with human A2B receptor cDNA, inhibition of agonist-induced cyclic AMP production was measured. An N5-(2-iodophenyl)acetyl derivative was highly selective for A2A receptors. An (R)-N5-alpha-methyl(phenylacetyl) derivative was the most potent derivative at A3 receptors, with a Ki value of 0.36 nM. A bulky N5-diphenylacetyl derivative, 13, displayed a Ki value of 0. 59 nM at human A3 receptors and was moderately selective for that subtype. Thus, a large, nondiscriminating hydrophobic region occurs in the A3 receptor in proximity to the N5-substituent. A series of straight-chain N5-aminoalkylacyl derivatives demonstrated that for A2B receptors the optimal chain length occurs with three methylene groups, i.e., the N5-gamma-aminobutyryl derivative 27 which had a pA2 value of 8.0 but was not selective for A2B receptors. At A1, A2A, and A3 receptors however the optimum occurs with four methylene groups. An N5-pivaloyl derivative, which was less potent than 27 at A1, A2A, and A3 receptors, retained moderate potency at A2B receptors. A molecular model of the 27-A2B receptor complex based on the structure of rhodopsin utilizing a "cross-docking" procedure was developed in order to visualize the environment of the ligand binding site.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.