New 9-methyl-8-(4-hydroxyphenyl)adenine derivatives as A1 adenosine receptor antagonists

2011 ◽  
Vol 76 (11) ◽  
pp. 1379-1393 ◽  
Author(s):  
Catia Lambertucci ◽  
Michela Buccioni ◽  
Barbara Cacciari ◽  
Diego Dal Ben ◽  
Stephanie Federico ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Binding Assay ◽  
Radioligand Binding ◽  
Functional Assay ◽  
Receptor Subtypes ◽  
A1 Adenosine Receptor ◽  
Nanomolar Range ◽  
Mouse Ileum ◽  
Good Agreement ◽  
Adenine Derivatives

A new series of 9-methyladenines, bearing different bulky groups at the 8-position, were prepared and their affinity for the four human adenosine receptor subtypes were evaluated. All the synthesized compounds showed affinities at the A1, A2A, and A3AR subtypes ranging from nanomolar to micromolar levels with different degrees of A1selectivity, while they resulted nearly inactive at A2BAR. In particular, 9-methyl-8-[4-(4-methylbenzyloxy)phenyl]- adenine showed A1AR affinity in the nanomolar range and good levels of selectivity versus the other receptor subtypes. Furthermore, a functional assay at mouse ileum allowed to assess the potency of selected compounds at A1AR subtype. Results showed that all the tested derivatives are neutral antagonists and theirKbvalues are in good agreement with theKivalues from radioligand binding assay at human A1AR, confirming that the effect is due to inhibition of this subtype.

scholarly journals Discovery of benzothiazolylquinoline conjugates as novel human A 3 receptor antagonists: biological evaluations and molecular docking studies

2018 ◽  
Vol 5 (2) ◽  
pp. 171622 ◽  
Author(s):  
Bidisha Sarkar ◽  
Santanu Maiti ◽  
Gajanan Raosaheb Jadhav ◽  
Priyankar Paira
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Radioligand Binding ◽  
Physiological Responses ◽  
Docking Studies ◽  
Receptor Subtypes ◽  
Binding Data ◽  
Major Interest

Adenosine is known as an endogenous purine nucleoside and it modulates a wide variety of physiological responses by interacting with adenosine receptors. Among the four adenosine receptor subtypes, the A 3 receptor is of major interest in this study as it is overexpressed in some cancer cell lines. Herein, we have highlighted the strategy of designing the h A 3 receptor targeted novel benzothiazolylquinoline scaffolds. The radioligand binding data of the reported compounds are rationalized with the molecular docking results. Compound 6a showed best potency and selectivity at h A 3 among other adenosine receptors.

scholarly journals Nucleoside Prodrugs of A3 Adenosine Receptor Agonists and Antagonists

2006 ◽  
Vol 71 (6) ◽  
pp. 912-928 ◽  
Author(s):  
Pedro Besada ◽  
Liaman K. Mamedova ◽  
Krishnan K. Palaniappan ◽  
Zhan-Guo Gao ◽  
Bhalchandra V. Joshi ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Radioligand Binding ◽  
Parent Compound ◽  
Parent Drug ◽  
Biologically Active ◽  
Functional Assay ◽  
Adenosine Receptor Agonists ◽  
A3 Adenosine Receptor ◽  
Future Evaluation

9-(β-D-Ribosfuranosyluronamide)adenine derivatives that are selective agonists and antagonists of the A3 adenosine receptor (AR) have been derivatized as prodrugs for in vivo delivery. The free hydroxy groups at the 2' and 3' positions of the agonists 2-chloro-N6-(3-iodobenzyl)-9-(N-methyl-(β-D-ribosfuranosyluronamide)adenine 2b, the corresponding 4'-thio nucleoside 2c, and antagonists 4a and 4b (5'-N,N-dimethylamides related to 2b and 2c, respectively) were derivatized through simple acylation reactions. The prodrug derivatives were tested in radioligand binding assays at ARs and in a functional assay of adenylate cyclase at the A3AR and found to be considerably less active than the parent drugs. The hydrolysis of nucleoside 2',3'-diesters to regenerate the parent compound in the presence of human blood was demonstrated. 2',3'-Dipropionate esters of 2b and 4a were readily cleaved in a two-step reaction to regenerate the parent drug, on a time scale of two hours. The cleavage of a 2',3'-dihexanoate ester occurred at a slower rate. This indicates that the prodrugs are suitable as masked forms of the biologically active A3AR agonists and antagonists for future evaluation in vivo.

Pharmacology and Therapeutic Applications of A1 Adenosine Receptor Ligands

2003 ◽  
Vol 3 (4) ◽  
pp. 369-385 ◽  
Author(s):  
Arvinder Dhalla ◽  
John Shryock ◽  
Revati Shreeniwas ◽  
Luiz Belardinelli
Keyword(s):  
Adenosine Receptor ◽  
Receptor Ligands ◽  
A1 Adenosine Receptor ◽  
Therapeutic Applications ◽  
Adenosine Receptor Ligands
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