%0 Journal Article %1 Novellino2005 %A Novellino, E. %A Cosimelli, B. %A Ehlardo, M. %A Greco, G. %A Iadanza, M. %A Lavecchia, A. %A Rimoli, M. G. %A Sala, A. %A Settimo, A. Da %A Primofiore, G. %A Settimo, F. Da %A Taliani, S. %A Motta, C. La %A Klotz, K. N. %A Tuscano, D. %A Trincavelli, M. L. %A Martini, C. %D 2005 %J J Med Chem %K & *Databases, A1/*antagonists A2A/metabolism A3/*antagonists Adenosine Adenosine-5'-(N-ethylcarboxamide)/metabolism Adenosine/analogs Animals Benzimidazoles/*chemical Binding, CHO Competitive Cricetinae Design Drug Factual Humans Quinoxalines/*chemical Xanthines/metabolism derivatives/metabolism inhibitors/chemistry/metabolism synthesis/chemistry Receptor Cell %N 26 %P 8253-60 %T 2-(Benzimidazol-2-yl)quinoxalines: a novel class of selective antagonists at human A(1) and A(3) adenosine receptors designed by 3D database searching %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16366607 %V 48 %X The Cambridge Structural Database (CSD) was searched through two 3D queries based on substructures shared by well-known antagonists at the A(1) and A(3) adenosine receptors (ARs). Among the resulting 557 hits found in the CSD, we selected five compounds to purchase, synthesize, or translate synthetically into analogues better tailored to interact with the biological targets. Binding experiments using human ARs showed that four out of five tested compounds turned out to be antagonists at the A(1)AR or A(3)AR with K(i) values between 50 and 440 nM. Lead optimizations of 2-(benzimidazol-2-yl)quinoxalines (BIQs, 3) gave the best results in terms of potency and selectivity at the A(1) and A(3) ARs. Particularly, 2-(4-ethylthiobenzimidazol-2-yl)quinoxaline (3e) exhibited K(i) values at the A(1)AR, A(2A)AR, and A(3)AR of 0.5, 3440, and 955 nM, respectively, whereas 2-(4-methylbenzimidazol-2-yl)quinoxaline (3b) displayed at the same ARs K(i) values of 8000, 833, and 26 nM, respectively.

@article{Novellino2005, abstract = {The Cambridge Structural Database (CSD) was searched through two 3D queries based on substructures shared by well-known antagonists at the A(1) and A(3) adenosine receptors (ARs). Among the resulting 557 hits found in the CSD, we selected five compounds to purchase, synthesize, or translate synthetically into analogues better tailored to interact with the biological targets. Binding experiments using human ARs showed that four out of five tested compounds turned out to be antagonists at the A(1)AR or A(3)AR with K(i) values between 50 and 440 nM. Lead optimizations of 2-(benzimidazol-2-yl)quinoxalines (BIQs, 3) gave the best results in terms of potency and selectivity at the A(1) and A(3) ARs. Particularly, 2-(4-ethylthiobenzimidazol-2-yl)quinoxaline (3e) exhibited K(i) values at the A(1)AR, A(2A)AR, and A(3)AR of 0.5, 3440, and 955 nM, respectively, whereas 2-(4-methylbenzimidazol-2-yl)quinoxaline (3b) displayed at the same ARs K(i) values of 8000, 833, and 26 nM, respectively.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Novellino, E. and Cosimelli, B. and Ehlardo, M. and Greco, G. and Iadanza, M. and Lavecchia, A. and Rimoli, M. G. and Sala, A. and Settimo, A. Da and Primofiore, G. and Settimo, F. Da and Taliani, S. and Motta, C. La and Klotz, K. N. and Tuscano, D. and Trincavelli, M. L. and Martini, C.}, biburl = {https://www.bibsonomy.org/bibtex/288d8ab95f13fdfa4344b24f4193c2035/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {d8803dddf24ceb99cab24f33b841258e}, intrahash = {88d8ab95f13fdfa4344b24f4193c2035}, issn = {0022-2623 (Print) 0022-2623 (Linking)}, journal = {J Med Chem}, keywords = {& *Databases, A1/*antagonists A2A/metabolism A3/*antagonists Adenosine Adenosine-5'-(N-ethylcarboxamide)/metabolism Adenosine/analogs Animals Benzimidazoles/*chemical Binding, CHO Competitive Cricetinae Design Drug Factual Humans Quinoxalines/*chemical Xanthines/metabolism derivatives/metabolism inhibitors/chemistry/metabolism synthesis/chemistry Receptor Cell}, month = {Dec 29}, note = {Novellino, Ettore Cosimelli, Barbara Ehlardo, Marina Greco, Giovanni Iadanza, Manuela Lavecchia, Antonio Rimoli, Maria Grazia Sala, Annalisa Da Settimo, Antonio Primofiore, Giampaolo Da Settimo, Federico Taliani, Sabrina La Motta, Concettina Klotz, Karl-Norbert Tuscano, Daniela Trincavelli, Maria Letizia Martini, Claudia Research Support, Non-U.S. Gov't United States Journal of medicinal chemistry J Med Chem. 2005 Dec 29;48(26):8253-60.}, number = 26, pages = {8253-60}, shorttitle = {2-(Benzimidazol-2-yl)quinoxalines: a novel class of selective antagonists at human A(1) and A(3) adenosine receptors designed by 3D database searching}, timestamp = {2010-12-14T18:20:40.000+0100}, title = {2-(Benzimidazol-2-yl)quinoxalines: a novel class of selective antagonists at human A(1) and A(3) adenosine receptors designed by 3D database searching}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16366607}, volume = 48, year = 2005 }