%0 Journal Article %1 Vittori2004 %A Vittori, S. %A Costanzi, S. %A Lambertucci, C. %A Portino, F. R. %A Taffi, S. %A Volpini, R. %A Klotz, K. N. %A Cristalli, G. %D 2004 %J Nucleosides Nucleotides Nucleic Acids %K & A2B/*agonists Adenosine Adenosine-5'-(N-ethylcarboxamide)/*analogs Adenosine/analogs Animals Assay CHO Cricetinae Humans Ligands Radioligand derivatives/*chemical derivatives/chemical synthesis/pharmacology Receptor Cell %N 1-2 %P 471-81 %T A2B adenosine receptor agonists: synthesis and biological evaluation of 2-phenylhydroxypropynyl adenosine and NECA derivatives %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15043167 %V 23 %X In the search for agonists for the elusive A2B adenosine receptor subtypes, 2-phenylhydroxypropynyl-5'-N-methylcarboxamido adenosine (PHPMECA, 14), 2-phenylhydroxypropynyl-5'-N-propylcarboxamido adenosine (PHPPECA, 15), and N6-ethyl-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine (19) were synthesized on the basis that introduction of alkynyl chains in 2-position of adenosine derivatives resulted in reasonably good A2B potency compared to NECA see N6-ethyl-2-phenylhydroxypropynyl adenosine (5) EC50 = 1,700 nM and 2-phenylhydroxypropynyl-5'-N-ethylcarboxamido adenosine (PHPNECA, 8) EC50 = 1,100 nM, respectively. Radioligand binding studies and adenylyl cyclase assays, performed with recently cloned human A1, A2A, A2B, and A3 adenosine receptors, showed that these modifications produced a decrease in potency at A2B receptor, as well as a general reduction in affinity at the other receptor subtypes. On the other hand, the contemporary presence of an ethyl substituent in N6-position and of a 4'-ethylcarboxamido group in the same compounds led to (R,S)-N6-ethyl-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine and (S)-N6-ethyl-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine, which did not show the expected increase in potency at A2B subtype. Hence, (S)-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine (S)-PHPNECA with EC50 A2B = 220 nM remains the most potent agonist at A2B receptor reported so far.

@article{Vittori2004, abstract = {In the search for agonists for the elusive A2B adenosine receptor subtypes, 2-phenylhydroxypropynyl-5'-N-methylcarboxamido adenosine (PHPMECA, 14), 2-phenylhydroxypropynyl-5'-N-propylcarboxamido adenosine (PHPPECA, 15), and N6-ethyl-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine (19) were synthesized on the basis that introduction of alkynyl chains in 2-position of adenosine derivatives resulted in reasonably good A2B potency compared to NECA [see N6-ethyl-2-phenylhydroxypropynyl adenosine (5) EC50 = 1,700 nM and 2-phenylhydroxypropynyl-5'-N-ethylcarboxamido adenosine (PHPNECA, 8) EC50 = 1,100 nM, respectively]. Radioligand binding studies and adenylyl cyclase assays, performed with recently cloned human A1, A2A, A2B, and A3 adenosine receptors, showed that these modifications produced a decrease in potency at A2B receptor, as well as a general reduction in affinity at the other receptor subtypes. On the other hand, the contemporary presence of an ethyl substituent in N6-position and of a 4'-ethylcarboxamido group in the same compounds led to (R,S)-N6-ethyl-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine and (S)-N6-ethyl-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine, which did not show the expected increase in potency at A2B subtype. Hence, (S)-2-phenylhydroxypropynyl-5'-N-ethylcarboxamidoadenosine [(S)-PHPNECA] with EC50 A2B = 220 nM remains the most potent agonist at A2B receptor reported so far.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Vittori, S. and Costanzi, S. and Lambertucci, C. and Portino, F. R. and Taffi, S. and Volpini, R. and Klotz, K. N. and Cristalli, G.}, biburl = {https://www.bibsonomy.org/bibtex/2538c5097e50d32e4ee4192feb9abb67c/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {53eb026a057112c5c8310c29987b8d03}, intrahash = {538c5097e50d32e4ee4192feb9abb67c}, issn = {1525-7770 (Print) 1525-7770 (Linking)}, journal = {Nucleosides Nucleotides Nucleic Acids}, keywords = {& A2B/*agonists Adenosine Adenosine-5'-(N-ethylcarboxamide)/*analogs Adenosine/analogs Animals Assay CHO Cricetinae Humans Ligands Radioligand derivatives/*chemical derivatives/chemical synthesis/pharmacology Receptor Cell}, note = {Vittori, S Costanzi, S Lambertucci, C Portino, F R Taffi, S Volpini, R Klotz, K N Cristalli, G Research Support, Non-U.S. Gov't United States Nucleosides, nucleotides \& nucleic acids Nucleosides Nucleotides Nucleic Acids. 2004;23(1-2):471-81.}, number = {1-2}, pages = {471-81}, shorttitle = {A2B adenosine receptor agonists: synthesis and biological evaluation of 2-phenylhydroxypropynyl adenosine and NECA derivatives}, timestamp = {2010-12-14T18:20:41.000+0100}, title = {A2B adenosine receptor agonists: synthesis and biological evaluation of 2-phenylhydroxypropynyl adenosine and NECA derivatives}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15043167}, volume = 23, year = 2004 }