A functional screening of adenosine analogues at the adenosine A2B receptor: a search for potent agonists.
Various adenosine analogues were tested at the adenosine A2B receptor. Agonist potencies were determined by measuring the cyclic AMP production in Chinese Hamster Ovary cells expressing human A2B receptors. 5'-N-Substituted carboxamidoadenosines were most potent. 5'-N-Ethylcarboxamidoadenosine (NECA) was most active with an EC50 value of 3.1 microM. Other ribose modified derivatives displayed low to negligible activity. Potency was reduced by substitution on the exocyclic amino function (N6) of the purine ring system. The most active N6-substituted derivative N6-methyl-NECA was 5 fold less potent than NECA. C8- and most C2-substituted analogues were virtually inactive. 1-Deaza-analogues had a reduced potency, 3- and 7-deazaanalogues were not active.
Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
M
M
de Zwart
R
R
Link
J K
JK
von Frijtag Drabbe Künzel
G
G
Cristalli
K A
KA
Jacobson
A
A
Townsend-Nicholson
A P
AP
IJzerman
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D058906:Purinergic P1 Receptor Agonists; D043704:Receptor, Adenosine A2B; D011994:Recombinant Proteins / Q000819:agonists
D058906:Purinergic P1 Receptor Agonists; D043704:Receptor, Adenosine A2B; D011994:Recombinant Proteins; C046756:5'-N-methylcarboxamideadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000241:Adenosine