کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1358032 | 981307 | 2014 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and evaluation of N6-substituted apioadenosines as potential adenosine A3 receptor modulators Synthesis and evaluation of N6-substituted apioadenosines as potential adenosine A3 receptor modulators](/preview/png/1358032.png)
Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A3AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of β-d-apio-d-furano- and α-d-apio-l-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N6 of β-d-apio-d-furanoadenosine afforded an A3AR antagonist (10c, Ki = 0.98 μM), while a similar modification of an α-d-apio-l-furanoadenosine gave rise to a partial agonist (11c, Ki = 3.07 μM). The structural basis for this difference was examined by docking to an A3AR model; the antagonist lacked a crucial interaction with Thr94.
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Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 15, 1 August 2014, Pages 4257–4268