title: Design and synthesis of N(6)-substituted-4'-thioadenosine-5'-uronamides as potent and selective human A(3) adenosine receptor agonists.
abstract: On the basis of a bioisosteric rationale, 4'-thionucleoside analogues of IB-MECA (N(6)-(3-Iodo-benzyl)-9-(5'-methylaminocarbonyl-beta-d-ribofuranosyl)adenine), which is a potent and selective A(3) adenosine receptor (AR) agonist, were synthesized from d-gulonic acid gamma-lactone. The 4'-thio analogue (5h) of IB-MECA showed extremely high binding affinity (K(i)=0.25 nM) at the human A(3)AR and was more potent than IB-MECA (K(i)=1.4 nM). Bulky substituents at the 5'-uronamide position, such as cyclohexyl and 2-methylbenzyl, in this series of 2-H nucleoside derivatives were tolerated in A(3)AR binding, although small alkyl analogues were more potent.
authors.affiliation: Department of Bioinspired Science and Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Choi
authors.forename: Hyuk Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Moshe
authors.initials: M
authors.lastname: Chinn
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Amit
authors.initials: A
authors.lastname: Patel
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Jung
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
mesh_terms: D058909:Adenosine A3 Receptor Agonists; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D011869:Radioligand Assay; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D058909:Adenosine A3 Receptor Agonists; D000577:Amides; D013872:Thionucleosides