title: Discovery of a new nucleoside template for human A3 adenosine receptor ligands: D-4'-thioadenosine derivatives without 4'-hydroxymethyl group as highly potent and selective antagonists.
abstract: Truncated D-4'-thioadenosine derivatives lacking the 4'-hydroxymethylene moiety were synthesized starting from D-mannose, using cyclization to the 4-thiosugar and one-step conversion of the diol to the acetate as key steps. At the human A3 adenosine receptor (AR), N6-substituted purine analogues bound potently and selectively and acted as antagonists in a cyclic AMP functional assay. An N6-(3-chlorobenzyl)purine analogue 9b displayed a Ki value of 1.66 nM at the human A3 AR. Thus, truncated D-4'-thioadenosine is an excellent template for the design of novel A3 AR antagonists to act at both human and murine species.
authors.affiliation: Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. lakjeong@ewha.ac.kr
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Choe
authors.forename: Prashantha
authors.initials: P
authors.lastname: Gunaga
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Hyuk Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Tosh
authors.forename: Amit
authors.initials: A
authors.lastname: Patel
authors.forename: Krishnan K
authors.initials: KK
authors.lastname: Palaniappan
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008024:Ligands; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013872:Thionucleosides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D008024:Ligands; D043684:Receptor, Adenosine A3; D013872:Thionucleosides; C050070:4'-thioadenosine; D000241:Adenosine