Synthesis and evaluation of N?-substituted apioadenosines as potential adenosine A? receptor modulators.

ABSTRACT: Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A?AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of ?-D-apio-D-furano- and ?-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N(6) of ?-D-apio-D-furanoadenosine afforded an A?AR antagonist (10c, Ki=0.98 ?M), while a similar modification of an ?-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, Ki=3.07 ?M). The structural basis for this difference was examined by docking to an A?AR model; the antagonist lacked a crucial interaction with Thr94.

SUBMITTER: Toti KS 

PROVIDER: S-EPMC4128473 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature