title: 5'-C-Ethyl-tetrazolyl-N(6)-substituted adenosine and 2-chloro-adenosine derivatives as highly potent dual acting A1 adenosine receptor agonists and A3 adenosine receptor antagonists.
abstract: A series of N(6)-substituted-5'-C-(2-ethyl-2H-tetrazol-5-yl)-adenosine and 2-chloro-adenosine derivatives was synthesized as novel, highly potent dual acting hA1AR agonists and hA3AR antagonists, potentially useful in the treatment of glaucoma and other diseases. The best affinity and selectivity profiles were achieved by N(6)-substitution with a 2-fluoro-4-chloro-phenyl- or a methyl- group. Through an in silico receptor-driven approach, the molecular bases of the hA1- and hA3AR recognition and activation of this series of 5'-C-ethyl-tetrazolyl derivatives were explained.
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Petrelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Torquati
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Palmarisa
authors.initials: P
authors.lastname: Franchetti
authors.forename: Mario
authors.initials: M
authors.lastname: Grifantini
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.forename: Loredana
authors.initials: L
authors.lastname: Cappellacci
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D058907:Adenosine A1 Receptor Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D058918:Adenosine A3 Receptor Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011869:Radioligand Assay; D043682:Receptor, Adenosine A1 / Q000737:chemistry*; D043684:Receptor, Adenosine A3 / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043684:Receptor, Adenosine A3; D000241:Adenosine