title: Design and synthesis of truncated 4'-thioadenosine derivatives as potent and selective A3 adenosine receptor antagonists.
abstract: We have established structure-activity relationships of novel truncated D-4'-thioadenosine derivatives from D-mannose as potent and selective A(3) adenosine receptor (AR) antagonists. At the human A(3) AR, most of N(6)-substituted analogues showed high potency and selectivity and acted as pure antagonists in a cyclic AMP functional assay. Among compounds tested, 2-chloro-N(6)-3-chlorobenzyl and N(6)-3-chlorobenzyl analogues displayed very high binding affinities (K(i) = 1.66 nM and 1.5 nM, respectively) at the human A(3) AR. Truncated 4'-thioadenosine derivatives studied here are regarded as an excellent template for the design of novel A(3) 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.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Hou
authors.forename: Shantanu
authors.initials: S
authors.lastname: Pal
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Choi
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Amol
authors.initials: A
authors.lastname: Tipnis
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D015195:Drug Design; D006801:Humans; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013872:Thionucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D043684:Receptor, Adenosine A3; D013872:Thionucleosides; C050070:4'-thioadenosine; D000241:Adenosine
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