Structure-activity relationships of truncated D- and l-4'-thioadenosine derivatives as species-independent A3 adenosine receptor antagonists.
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.
Jeong
Lak Shin
LS
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. lakjeong@ewha.ac.kr
Pal
Shantanu
S
Choe
Seung Ah
SA
Choi
Won Jun
WJ
Jacobson
Kenneth A
KA
Gao
Zhan-Guo
ZG
Klutz
Athena M
AM
Hou
Xiyan
X
Kim
Hea Ok
HO
Lee
Hyuk Woo
HW
Lee
Sang Kook
SK
Tosh
Dilip K
DK
Moon
Hyung Ryong
HR
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*
D058918:Adenosine A3 Receptor Antagonists; D043684:Receptor, Adenosine A3; D013872:Thionucleosides; C050070:4'-thioadenosine; D000241:Adenosine