title: Structure-activity relationships of truncated D- and l-4'-thioadenosine derivatives as species-independent A3 adenosine receptor antagonists.
abstract: Novel D- and l-4'-thioadenosine derivatives lacking the 4'-hydroxymethyl moiety were synthesized, starting from d-mannose and d-gulonic gamma-lactone, respectively, as potent and selective species-independent A 3 adenosine receptor (AR) antagonists. Among the novel 4'-truncated 2-H nucleosides tested, a N(6)-(3-chlorobenzyl) derivative 7c was the most potent at the human A 3 AR (K i = 1.5 nM), but a N(6)-(3-bromobenzyl) derivative 7d showed the optimal species-independent binding affinity.
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: Shantanu
authors.initials: S
authors.lastname: Pal
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Choe
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Choi
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Athena M
authors.initials: AM
authors.lastname: Klutz
authors.forename: Xiyan
authors.initials: X
authors.lastname: Hou
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: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D043684:Receptor, Adenosine A3; D013872:Thionucleosides; C050070:4'-thioadenosine; D000241:Adenosine