%0 Journal Article %1 Cristalli1992 %A Cristalli, G. %A Eleuteri, A. %A Vittori, S. %A Volpini, R. %A Lohse, M. J. %A Klotz, K. N. %D 1992 %J J Med Chem %K & Adenosine-5'-(N-ethylcarboxamide) Adenosine/*analogs Adenylate Aggregation/drug Animals Assay Binding, Blood Brain Cell Chemistry Competitive Cultured Cyclase/metabolism Humans Membrane/chemistry Platelet Platelets/chemistry Purinergic/*drug Radioligand Rats derivatives/chemistry/metabolism/*pharmacology effects Receptor %N 13 %P 2363-8 %T 2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamide as selective agonists at A2 adenosine receptors %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1619615 %V 35 %X In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A2 receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cyclase, and platelet aggregation studies. Binding of 3HNECA to A2 receptors of rat striatal membranes was inhibited by compounds 2a-d with Ki values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affinity binding at solubilized A2 receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand 3HDPCPX and for the agonist 3HCCPA gave Ki values in the nanomolar range, and the compounds showed moderate A2 selectivity. In order to improve this selectivity, the corresponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. As expected, the 5'-N-ethyluronamide derivatives retained the A2 affinity whereas the A1 affinity was attenuated, resulting in an up to 10-fold increase in A2 selectivity. A similar pattern was observed in adenylate cyclase assays and in platelet aggregation studies. A 30- to 45-fold selectivity for platelet A2 receptors compared to A1 receptors was found for compounds 8a-c in adenylate cyclase studies.

@article{Cristalli1992, abstract = {In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A2 receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cyclase, and platelet aggregation studies. Binding of [3H]NECA to A2 receptors of rat striatal membranes was inhibited by compounds 2a-d with Ki values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affinity binding at solubilized A2 receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [3H]DPCPX and for the agonist [3H]CCPA gave Ki values in the nanomolar range, and the compounds showed moderate A2 selectivity. In order to improve this selectivity, the corresponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. As expected, the 5'-N-ethyluronamide derivatives retained the A2 affinity whereas the A1 affinity was attenuated, resulting in an up to 10-fold increase in A2 selectivity. A similar pattern was observed in adenylate cyclase assays and in platelet aggregation studies. A 30- to 45-fold selectivity for platelet A2 receptors compared to A1 receptors was found for compounds 8a-c in adenylate cyclase studies.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Cristalli, G. and Eleuteri, A. and Vittori, S. and Volpini, R. and Lohse, M. J. and Klotz, K. N.}, biburl = {https://www.bibsonomy.org/bibtex/2e90ce832d9ef2b17d16845ec3258323a/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {b7f7469586df75c25275d3b48eb65051}, intrahash = {e90ce832d9ef2b17d16845ec3258323a}, issn = {0022-2623 (Print) 0022-2623 (Linking)}, journal = {J Med Chem}, keywords = {& Adenosine-5'-(N-ethylcarboxamide) Adenosine/*analogs Adenylate Aggregation/drug Animals Assay Binding, Blood Brain Cell Chemistry Competitive Cultured Cyclase/metabolism Humans Membrane/chemistry Platelet Platelets/chemistry Purinergic/*drug Radioligand Rats derivatives/chemistry/metabolism/*pharmacology effects Receptor}, month = {Jun 26}, note = {Cristalli, G Eleuteri, A Vittori, S Volpini, R Lohse, M J Klotz, K N Research Support, Non-U.S. Gov't United states Journal of medicinal chemistry J Med Chem. 1992 Jun 26;35(13):2363-8.}, number = 13, pages = {2363-8}, shorttitle = {2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamide as selective agonists at A2 adenosine receptors}, timestamp = {2010-12-14T18:20:48.000+0100}, title = {2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamide as selective agonists at A2 adenosine receptors}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1619615}, volume = 35, year = 1992 }