Non‐Xanthine Antagonists for the Adenosine A<sub>1</sub> Receptor

Chang, Lisa C. W.; Brussee, Johannes; IJzerman, Adriaan P.

doi:10.1002/cbdv.200490122

Cited by 18 publications

(23 citation statements)

References 125 publications

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“…(3)) [34]. 20,21,35]. Monocyclic heteroaromatic rings are relatively rarely found in adenosine A 1 receptor antagonism and have generally low affinity with the exception of two fivemembered heterocycles, thiazoles and thiadiazoles.…”

Section: A 1 Ar Xanthine Antagonistsmentioning

confidence: 99%

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

Yuzlenko

Kieć‐Kononowicz

2006

CMC

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This review summarizes the current tendencies observed in the past 5 years in the development of A(1) and A(2A) adenosine receptor antagonists performed in various academia and industry. A(1) and A(2A) AR antagonists are as well xanthines as heteroaromatic derivatives and are most commonly 6:5 fused heteroatomic compounds. Among xanthine-based compounds, some common features could be pointed out. The recent A(1) AR ligands which show good biological profile, possess long alkyl chains in position 1 and 3 as well as bulky C(8)-substituent, while A(2A) AR antagonists with a high A(2A) AR affinity are C(8)-styryl substituted with N(1)-alkyl/alkynyl moiety or fused tricyclic xanthines possessing heteroatom(s) in the third cycle. The research in the field of heteroaromatic A(1) and A(2A) ARs antagonists impressively has a wide range. Ligands are as well non-fused monocyclic substituted compounds as fused bi- and tricyclic derivatives with the nitrogen, oxygen and sulfur heteroatoms. Most often, adenosine A(1) receptor non-xanthine antagonists are adenine-based, having substituted amino group and variable nitrogen atoms positions in the molecules. A(2A) AR ligands show good affinity when furanyl function, which is crucial for binding, is present in the fused bicyclic and tricyclic analogs. Moreover, tricyclic nitrogen containing antagonists in order to be active, frequently possess long-alkylphenyl moiety.

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Section: A 1 Ar Xanthine Antagonistsmentioning

confidence: 99%

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

Yuzlenko

Kieć‐Kononowicz

2006

CMC

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“…Subsequently 13.4 mmol EDAC and 10 mmol phenylpropanoic acid (8) was added, the pH was adjusted to 5 with 4 N HCl and stirred for 2 h at room temperature. 1,3-dialkyl-7H-xanthine derivatives (11): To the 1,3-dialkyl-6-amino-5-carboxamidouracil (10) reaction mixture, 1 g of sodium hydroxide (dissolved in 1 mL H 2 O) was added.…”

Section: Synthetic Preparationmentioning

confidence: 99%

“…30 The xanthine scaffold may also be used to design compounds for adenosine A 1 receptor affinity. 8 Based on the above and the need to explore the adenosine A 1 receptor affinity, prompted us to explore further the adenosine A 1 and A 2A affinity of the latter reported xanthines. Furthermore, we introduced another aryl-substituent at position C8, namely 8-(2-phenylethyl).…”

Section: Introductionmentioning

confidence: 99%

“…The adenosine A 1 receptors are mainly involved as drug targets in renal conditions and cognitive deficits. 7,8 Adenosine A 1 receptors are widely expressed throughout the human brain, 9,10 including the hippocampus and pre-frontal cortex, that are considered important areas for cognitive function. 11 Post-mortem samples of AD patients showed a reduced density of adenosine A 1 receptors 12,13 and in animal studies the blockade of these receptors have been reported previously to enhance cognition in rodents.…”

Section: Introductionmentioning

confidence: 99%

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1,3,7-Triethyl-substituted xanthines—possess nanomolar affinity for the adenosine A1 receptor

Walt

Terre’Blanche

2015

Bioorganic & Medicinal Chemistry

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“…This assay followed the procedure described by Chang, Brussee, and IJzerman (2004), with a minor modification consisting of taking the final volume of the total mixture to 200 ll. The radioactive ligand used for the assay was 0.4 nM [ 3 H] DCPCX (8-cyclopentyl-1,3-dipropylxanthine) (K d = 1.6 nM).…”

Section: Adenosine A1 Receptor Assaymentioning

confidence: 99%