Synthesis of 3'-acetamidoadenosine derivatives as potential A3 adenosine receptor agonists.
On the basis of high binding affinity of 3'-aminoadenosine derivatives 2b at the human A3 adenosine receptor (AR), 3'-acetamidoadenosine derivatives 3a-e were synthesized from 1,2:5,6-di-O-isopropylidene-D-glucose via stereoselective hydroboration as a key step. Although all synthesized compounds were totally devoid of binding affinity at the human A3AR, our results revealed that 3'-position of adenosine can only be tolerated with small size of a hydrogen bonding donor like hydroxyl or amino group in the binding site of human A3AR.
Chun
Moon Woo
MW
College of Pharmacy, Seoul National University, Seoul, Korea. mwchun@snu.ac.kr
Choi
Sung Wook
SW
Kang
Tae Kyung
TK
Choi
Won Jun
WJ
Kim
Hea Ok
HO
Gao
Zhan-Guo
ZG
Jacobson
Kenneth A
KA
Jeong
Lak Shin
LS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D058909:Adenosine A3 Receptor Agonists; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D058909:Adenosine A3 Receptor Agonists; D043684:Receptor, Adenosine A3; D000241:Adenosine