%0 Journal Article %1 Cristalli1988 %A Cristalli, G. %A Franchetti, P. %A Grifantini, M. %A Vittori, S. %A Klotz, K. N. %A Lohse, M. J. %D 1988 %J J Med Chem %K & Adenosine-5'-(N-ethylcarboxamide) Adenosine/analogs Adenylate Agents/*pharmacology Aminoglycosides Animals Anti-Bacterial Cyclase/analysis Humans Purinergic/*drug Rats Relationship Structure-Activity Tubercidin/chemical derivatives/metabolism effects synthesis/*pharmacology Receptor %N 6 %P 1179-83 %T Adenosine receptor agonists: synthesis and biological evaluation of 1-deaza analogues of adenosine derivatives %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3373486 %V 31 %X In a search for more selective A1 adenosine receptor agonists, N6-(R)-(-)-1-methyl-2-phenethyl-1-deazaadenosine (1-deaza-R-PIA, 3a), N6-cyclopentyl-1-deazaadenosine (1-deazaCPA, 3b), N6-cyclohexyl-1-deazaadenosine (1-deazaCHA, 3c), and the corresponding 2-chloro derivatives 2a-c were synthesized from 5,7-dichloro-3-beta-D-ribofuranosyl-3H-imidazo4,5-bpyridine. On the other hand, N-ethyl-1'-deoxy-1'-(1-deaza-6-amino-9H-purin-9-yl)-beta-D-ribofuranu ronamide (1-deazaNECA, 10) was prepared from 7-nitro-3-beta-D-ribofuranosyl-3H-imidazo4,5-bpyridine, in an attempt to find a more selective A2 agonist. The activity of all deaza analogues at adenosine receptors has been determined in adenylate cyclase and in radioligand binding studies. 1-DeazaNECA proved to be a nonselective agonist at both subtypes of the adenosine receptor. It is about 10-fold less active than NECA but clearly more active than the parent compound 1-deazaadenosine as an inhibitor of platelet aggregation and as a stimulator of cyclic AMP accumulation. The N6-substituted 1-deazaadenosines largely retain the A1 agonist activity of their parent compounds, but lose some of their A2 agonist activity. This results in A1-selective compounds, of which N6-cyclopentyl-2-chloro-1-deazaadenosine (1-deaza-2-Cl-CPA, 2b) was identified as the most selective agonist at A1 adenosine receptors so far known. The activity of all 1-deaza analogues confirms that the presence of the nitrogen atom at position 1 of the purine ring is not critical for A1 receptor mediated adenosine actions.

@article{Cristalli1988, abstract = {In a search for more selective A1 adenosine receptor agonists, N6-[(R)-(-)-1-methyl-2-phenethyl]-1-deazaadenosine (1-deaza-R-PIA, 3a), N6-cyclopentyl-1-deazaadenosine (1-deazaCPA, 3b), N6-cyclohexyl-1-deazaadenosine (1-deazaCHA, 3c), and the corresponding 2-chloro derivatives 2a-c were synthesized from 5,7-dichloro-3-beta-D-ribofuranosyl-3H-imidazo[4,5-b]pyridine. On the other hand, N-ethyl-1'-deoxy-1'-(1-deaza-6-amino-9H-purin-9-yl)-beta-D-ribofuranu ronamide (1-deazaNECA, 10) was prepared from 7-nitro-3-beta-D-ribofuranosyl-3H-imidazo[4,5-b]pyridine, in an attempt to find a more selective A2 agonist. The activity of all deaza analogues at adenosine receptors has been determined in adenylate cyclase and in radioligand binding studies. 1-DeazaNECA proved to be a nonselective agonist at both subtypes of the adenosine receptor. It is about 10-fold less active than NECA but clearly more active than the parent compound 1-deazaadenosine as an inhibitor of platelet aggregation and as a stimulator of cyclic AMP accumulation. The N6-substituted 1-deazaadenosines largely retain the A1 agonist activity of their parent compounds, but lose some of their A2 agonist activity. This results in A1-selective compounds, of which N6-cyclopentyl-2-chloro-1-deazaadenosine (1-deaza-2-Cl-CPA, 2b) was identified as the most selective agonist at A1 adenosine receptors so far known. The activity of all 1-deaza analogues confirms that the presence of the nitrogen atom at position 1 of the purine ring is not critical for A1 receptor mediated adenosine actions.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Cristalli, G. and Franchetti, P. and Grifantini, M. and Vittori, S. and Klotz, K. N. and Lohse, M. J.}, biburl = {https://www.bibsonomy.org/bibtex/2ef530cbca4c47b294fa650ce79acf6d9/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {956cc028428c34c9ed9db9c0868f14db}, intrahash = {ef530cbca4c47b294fa650ce79acf6d9}, issn = {0022-2623 (Print) 0022-2623 (Linking)}, journal = {J Med Chem}, keywords = {& Adenosine-5'-(N-ethylcarboxamide) Adenosine/analogs Adenylate Agents/*pharmacology Aminoglycosides Animals Anti-Bacterial Cyclase/analysis Humans Purinergic/*drug Rats Relationship Structure-Activity Tubercidin/chemical derivatives/metabolism effects synthesis/*pharmacology Receptor}, month = Jun, note = {Cristalli, G Franchetti, P Grifantini, M Vittori, S Klotz, K N Lohse, M J Research Support, Non-U.S. Gov't United states Journal of medicinal chemistry J Med Chem. 1988 Jun;31(6):1179-83.}, number = 6, pages = {1179-83}, shorttitle = {Adenosine receptor agonists: synthesis and biological evaluation of 1-deaza analogues of adenosine derivatives}, timestamp = {2010-12-14T18:22:02.000+0100}, title = {Adenosine receptor agonists: synthesis and biological evaluation of 1-deaza analogues of adenosine derivatives}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3373486}, volume = 31, year = 1988 }