Unknown

Dataset Information

0

Discovery of New Human A(2A) Adenosine Receptor Agonists: Design, Synthesis, and Binding Mode of Truncated 2-Hexynyl-4'-thioadenosine.

ABSTRACT: The truncated C2- and C8-substituted-4'-thioadenosine derivatives 4a-d were synthesized from D-mannose, using palladium-catalyzed cross coupling reactions as key steps. In this study, an A(3) adenosine receptor (AR) antagonist, truncated 4'-thioadenosine derivative 3 was successfully converted into a potent A(2A)AR agonist 4a (K(i) = 7.19 ± 0.6 nM) by appending a 2-hexynyl group at the C2-position of a derivative of 3 that was N(6)-substituted. However, C8-substitution greatly reduced binding affinity at the human A(2A)AR. All synthesized compounds 4a-d maintained their affinity at the human A(3)AR, but 4a was found to be a competitive A(3)AR antagonist/A(2A)AR agonist in cyclic AMP assays. This study indicates that the truncated C2-substituted-4'-thioadenosine derivatives 4a and 4b can serve as a novel template for the development of new A(2A)AR ligands.

SUBMITTER: Hou X 

PROVIDER: S-EPMC3030271 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Discovery of New Human A(2A) Adenosine Receptor Agonists: Design, Synthesis, and Binding Mode of Truncated 2-Hexynyl-4'-thioadenosine.

Hou Xiyan X   Kim Hea Ok HO   Alexander Varughese V   Kim Kyunglim K   Choi Sun S   Park Seul-Gi SG   Lee Jin Hee JH   Yoo Lena S LS   Gao Zhan-Guo ZG   Jacobson Kenneth A KA   Jeong Lak Shin LS  

ACS medicinal chemistry letters 20100901 9

The truncated C2- and C8-substituted-4'-thioadenosine derivatives 4a-d were synthesized from D-mannose, using palladium-catalyzed cross coupling reactions as key steps. In this study, an A(3) adenosine receptor (AR) antagonist, truncated 4'-thioadenosine derivative 3 was successfully converted into a potent A(2A)AR agonist 4a (K(i) = 7.19 ± 0.6 nM) by appending a 2-hexynyl group at the C2-position of a derivative of 3 that was N(6)-substituted. However, C8-substitution greatly reduced binding af  ...[more]

Similar Datasets

Unknown Design, synthesis, and binding of homologated truncated 4'-thioadenosine derivatives at the human A3 adenosine receptors.
| S-EPMC3724522 | biostudies-literature
Unknown Structure-activity relationships of truncated D- and l-4'-thioadenosine derivatives as species-independent A3 adenosine receptor antagonists.
| S-EPMC3616494 | biostudies-literature
Unknown N6-substituted D-4'-thioadenosine-5'-methyluronamides: potent and selective agonists at the human A3 adenosine receptor.
| S-EPMC11770563 | biostudies-literature
Unknown Discovery of 1,2,4-triazine derivatives as adenosine A(2A) antagonists using structure based drug design.
| S-EPMC3308197 | biostudies-literature
Unknown Truncated (N)-Methanocarba Nucleosides as A(1) Adenosine Receptor Agonists and Partial Agonists: Overcoming Lack of a Recognition Element.
| S-EPMC3156476 | biostudies-literature
Unknown Adenosine A(2A) Receptor Binding Profile of Two Antagonists, ST1535 and KW6002: Consideration on the Presence of Atypical Adenosine A(2A) Binding Sites.
| S-EPMC3059644 | biostudies-literature
Unknown Discovery of the First Efficacious Adenosine 2A Receptor Negative Allosteric Modulators for High Adenosine Cancer Immunotherapies.
| S-EPMC11873987 | biostudies-literature
Unknown Structure-based discovery of novel chemotypes for adenosine A(2A) receptor antagonists.
| S-EPMC2826142 | biostudies-literature
Unknown 2,3-Dihydro-1-benzofuran derivatives as a series of potent selective cannabinoid receptor 2 agonists: design, synthesis, and binding mode prediction through ligand-steered modeling.
| S-EPMC3262993 | biostudies-literature
Unknown Identification of an adenosine receptor domain specifically involved in binding of 5'-substituted adenosine agonists.
| S-EPMC5470540 | biostudies-literature