title: Synthesis of 2-chloro-N6-substituted-4'-thioadenosine-5'-N, N-dialkyluronamides as potent and selective A3 adenosine receptor antagonists.
abstract: The highly selective A(3) receptor agonist, 4'-thio-Cl-IB-MECA was successfully converted into selective A(3) receptor antagonists by appending a second N-alkyl group on the 5'-uronamide position. This result indicates that the hydrogen bonding ability of the 5'-uronamide is essential for the conformational change required for the receptor activation. Among compounds tested, a N(6)-(3-bromobenzyl) derivative with 5'-dimethyluronamide exhibited the highest binding affinity (K(i) = 9.32 nM) at the human A(3) AR with very low binding affinities to other AR subtypes.
authors.affiliation: Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Choi
authors.forename: Hyuk Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Xiyan
authors.initials: X
authors.lastname: Hou
authors.forename: Hea O K
authors.initials: HO
authors.lastname: Kim
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; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006860:Hydrogen Bonding; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D011684:Purine Nucleosides; D043684:Receptor, Adenosine A3; C504222:thio-Cl-IB-MECA; D000241:Adenosine
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