Design, synthesis and binding affinity of 3'-fluoro analogues of Cl-IB-MECA as adenosine A3 receptor ligands.
Several 3'-fluoro analogues, 1a, 1b, and 1c of selective and potent adenosine A(3) receptor agonist, Cl-IB-MECA were synthesized from D-xylose via highly regioselective opening of lyxo-epoxides, 8a and 8b with fluoride anion. Compared to the high binding affinity of Cl-IB-MECA to the A(3) adenosine receptor, the corresponding 3'-fluoro derivative showed remarkably decreased binding affinity, indicating that 3'-hydroxyl group acts as hydrogen bonding acceptor, not hydrogen bonding donor like fluorine atom in binding to the A(3) adenosine receptor.
Lim
Moo Hong
MH
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Kim
Hea Ok
HO
Moon
Hyung Ryong
HR
Lee
Seung Jin
SJ
Chun
Moon Woo
MW
Gao
Zhan-Guo
ZG
Melman
Neli
N
Jacobson
Kenneth A
KA
Kim
Joong Hyup
JH
Jeong
Lak Shin
LS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015195:Drug Design; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D058906:Purinergic P1 Receptor Agonists; D011869:Radioligand Assay; D051381:Rats; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000819:agonists / Q000378:metabolism; D013329:Structure-Activity Relationship
D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D011994:Recombinant Proteins; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide