title: N6-substituted D-4'-thioadenosine-5'-methyluronamides: potent and selective agonists at the human A3 adenosine receptor.
abstract: 4'-Thio analogues 3-5 of Cl-IB-MECA (2) (K(i) = 1.0 +/- 0.2 nM at the human A(3) adenosine receptor) were synthesized from d-gulono-gamma-lactone via 4-thioribosyl acetate 14 as the key intermediate. All synthesized 4'-thionucleosides exhibited higher binding affinity to the human A(3) adenosine receptor than Cl-IB-MECA, among which 4 showed the most potent binding affinity (K(i) = 0.28 +/- 0.09 nM). 4 was also selective for A(3) vs human A(1) and human A(2A) receptors by 4800- and 36000-fold, respectively.
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: Dong Zhe
authors.initials: DZ
authors.lastname: Jin
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Dae Hong
authors.initials: DH
authors.lastname: Shin
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Prashantha
authors.initials: P
authors.lastname: Gunaga
authors.forename: Moon Woo
authors.initials: MW
authors.lastname: Chun
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Neli
authors.initials: N
authors.lastname: Melman
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D058906:Purinergic P1 Receptor Agonists; D011869:Radioligand Assay; D051381:Rats; D043684:Receptor, Adenosine A3; D013329:Structure-Activity Relationship; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008024:Ligands; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D013872:Thionucleosides; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide