Title: 8-Substituted adenosine and theophylline-7-riboside analogues as potential partial agonists for the adenosine A1 receptor
Authors: Van der Wenden, E M ×
Hartog-Witte, H R
Roelen, H C P F
von Frijtag Drabbe Künzel, J K
Pirovano, I M
Mathôt, R A A
Danhof, M
Van Aerschot, Arthur
Lidaks, M J
IJzerman, A P
Soudijn, W #
Issue Date: Aug-1995
Publisher: Elsevier science bv
Series Title: European journal of pharmacology vol:290 issue:3 pages:189-199
Abstract: A series of 8-substituted adenosine and theophylline-7-riboside analogues (28 and 9 compounds, respectively) was tested on adenosine A1 and A2A receptors as an extensive exploration of the adenosine C8-region. Alkylamino substituents at the 8-position cause an affinity decrease for adenosine analogues, but an affinity increase for theophylline-7-riboside derivatives. The affinity decrease is probably due to a direct steric hindrance between the C8-substituent and the binding site as well as to electronic effects, not to a steric influence on the ribose moiety to adopt the anti conformation. The 8-substituents increase the affinity of theophylline-7-riboside analogues probably by binding to a lipophilic binding site. The intrinsic activity was tested in vitro for some 8-substituted adenosine analogues, by determining the GTP shift in receptor binding studies and the inhibition of adenylate cyclase in a culture of rat thyroid FRTL-5 cells, and in vivo in the rat cardiovascular system for 8-butylaminoadenosine. Thus, it was shown that 8-ethyl-, 8-butyl-, and 8-pentylamino substituted analogues of adenosine may be partial agonists in vitro, and that 8-butylaminoadenosine is a partial agonist for the rat cardiovascular A1 receptor in vivo.
ISSN: 0922-4106
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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