N6-substituted D-4'-thioadenosine-5'-methyluronamides: potent and selective agonists at the human A3 adenosine receptor.
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.
Jeong
Lak Shin
LS
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. lakjeong@ewha.ac.kr
Jin
Dong Zhe
DZ
Kim
Hea Ok
HO
Shin
Dae Hong
DH
Moon
Hyung Ryong
HR
Gunaga
Prashantha
P
Chun
Moon Woo
MW
Kim
Yong-Chul
YC
Melman
Neli
N
Gao
Zhan-Guo
ZG
Jacobson
Kenneth A
KA
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
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