2 The Adenosine A3 Receptor and its Ligands

Muijlwijk‐Koezen, Jacqueline E. van; Timmerman, H.; IJzerman, Adriaan P.

doi:10.1016/s0079-6468(08)70092-4

Cited by 12 publications

(18 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chew WS et al (2016) To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling. Melanin-concentrating hormone receptors G protein-coupled receptors → Melanin-concentrating hormone receptors…”

Section: Further Reading On Lysophospholipid (S1p) Receptorsmentioning

confidence: 99%

THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein‐coupled receptors

Alexander

Christopoulos

Davenport

et al. 2017

British J Pharmacology

740

655

View full text Add to dashboard Cite

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13878/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate. Conflict of interestThe authors state that there are no conflicts of interest to declare.

show abstract

Section: Further Reading On Lysophospholipid (S1p) Receptorsmentioning

confidence: 99%

THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein‐coupled receptors

Alexander

Christopoulos

Davenport

et al. 2017

British J Pharmacology

740

655

View full text Add to dashboard Cite

show abstract

“…Similar phenyl substituents in the urea and benzamide series led to comparable affinities (comparison of 2-and 4-substituents and 3-substituents). 20 This suggests a common binding site for the benzamide and phenylurea substituents. The structures of 4-methoxy-N-[3-(2-pyridyl)isoquinolin-1-yl]benzamide (15) 20 and N- (2- Figure 2) were built and minimized.…”

Section: Resultsmentioning

confidence: 95%

“…20 This suggests a common binding site for the benzamide and phenylurea substituents. The structures of 4-methoxy-N-[3-(2-pyridyl)isoquinolin-1-yl]benzamide (15) 20 and N- (2- Figure 2) were built and minimized. From energy minimizations with molecular mechanics, four conformations emerged, each with the nitrogen of the pyridine ring "upwards", i.e., in the opposite direction of the spacer.…”

Section: Resultsmentioning

confidence: 95%

“…In our previous studies 20 it had been shown that isoquinolines differ only slightly from quinazolines in their affinities at adenosine receptors. To check whether this also held in the urea series, we synthesized and determined the affinity of quinazolines 5a,b,d and isoquinolines 8a,b,d ( Table 3).…”

Section: Resultsmentioning

confidence: 96%

“…10 For this reason library screening was used to search for novel leads. Triazolonaphthpyridine, 11,12 1,4-dihydropyridines [13][14][15] and pyridines, 16 triazoloquinazolines, 17,18 isoquinolines and quinazolines, 19,20 and flavonoids 21 were identified as adenosine A 3 receptor ligands this way, and chemical optimization of the leads yielded selective adenosine A 3 receptor antagonists.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Isoquinoline and Quinazoline Urea Analogues as Antagonists for the Human Adenosine A₃Receptor

et al. 2000

Self Cite

View full text Add to dashboard Cite

Isoquinoline and quinazoline urea derivatives were found to bind to human adenosine A 3 receptors. Series of N-phenyl-N′-quinazolin-4-ylurea derivatives and N-phenyl-N′-isoquinolin-1-ylurea derivatives were synthesized and tested in radioligand binding assays on their adenosine receptor affinities. A structure-affinity analysis indicated that on the 2-position of the quinazoline ring or the equivalent 3-position of the isoquinoline ring a phenyl or heteroaryl substituent increased the adenosine A 3 receptor affinity in comparison to unsubstituted or aliphatic derivatives. Furthermore, the structure-affinity relationship of substituted phenylurea analogues was investigated. Substituents such as electron-withdrawing or electron-donating groups were introduced at different positions of the benzene ring to probe electronic and positional effects of substitution. Substitution on the 3-or 4-position of the phenyl ring decreased the adenosine A 3 receptor affinity. Substitution at position 2 with an electron-donating substituent, such as methyl or methoxy, increased human adenosine A 3 receptor affinity, whereas substitution on the 2-position with an electron-withdrawing substituent did not influence affinity. Combination of the optimal substituents in the two series had an additive effect, which led to the potent human adenosine A 3 (VUF5574, 10a) showing a K i value of 4 nM and being at least 2500-fold selective vs A 1 and A 2A receptors. Compound 10a competitively antagonized the effect of an agonist in a functional A 3 receptor assay, i.e., inhibition of cAMP production in cells expressing the human adenosine A 3 receptor; a pA 2 value of 8.1 was derived from a Schild plot. In conclusion, compound 10a is a potent and selective human adenosine A 3 receptor antagonist and might be a useful tool in further characterization of the human A 3 receptor. receptor antagonist N-(2-methoxyphenyl)-N′-(2-(3-pyridyl)quinazolin-4-yl)urea

show abstract

Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?

González

Terán

Teijeira

2007

Medicinal Research Reviews

View full text Add to dashboard Cite

In view of the large libraries of nucleoside analogues that are now being handled in organic synthesis, the identification of drug biological activity is advisable prior to synthesis and this can be achieved by employing predictive biological property methods. In this sense, Quantitative Structure-Activity Relationships (QSAR) or docking approaches have emerged as promising tools. Although a large number of in silico approaches have been described in the literature for the prediction of different biological activities, the use of QSAR applications to develop adenosine receptor (AR) antagonists is not common as for the case of the antibiotics and anticancer compounds for instance. The intention of this review is to summarize the present knowledge concerning computational predictions of new molecules as adenosine receptor antagonists.

show abstract

2 The Adenosine A3 Receptor and its Ligands

Cited by 12 publications

References 141 publications

THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein‐coupled receptors

THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein‐coupled receptors

Isoquinoline and Quinazoline Urea Analogues as Antagonists for the Human Adenosine A₃Receptor

Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?

Contact Info

Product

Resources

About

2 The Adenosine A3 Receptor and its Ligands

Cited by 12 publications

References 141 publications

THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein‐coupled receptors

THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein‐coupled receptors

Isoquinoline and Quinazoline Urea Analogues as Antagonists for the Human Adenosine A3Receptor

Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?

Contact Info

Product

Resources

About

Isoquinoline and Quinazoline Urea Analogues as Antagonists for the Human Adenosine A₃Receptor