Design and synthesis of 3'-ureidoadenosine-5'-uronamides: effects of the 3'-ureido group on binding to the A3 adenosine receptor.
On the basis of high binding affinity at the A(3) adenosine receptor of 3'-aminoadenosine derivatives with hydrogen bonding donor ability, novel 3'-ureidoadenosine analogues were synthesized from 1,2:5,6-di-O-isopropylidene-d-glucose in order to lead to stronger hydrogen bonding than the corresponding 3'-aminoadenosine derivatives. However, the synthesized 3'-ureidoadenosine analogues were totally devoid of binding affinity, because 3'-urea moiety caused steric and electrostatic repulsions at the binding site of the A(3) adenosine receptor, leading to conformational distortion.
Jeong
Lak Shin
LS
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea. lakjeong@ewha.ac.kr
Kim
Myong Jung
MJ
Kim
Hea Ok
HO
Gao
Zhan-Guo
ZG
Kim
Soo-Kyung
SK
Jacobson
Kenneth A
KA
Chun
Moon Woo
MW
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D058909:Adenosine A3 Receptor Agonists; D001665:Binding Sites; D015195:Drug Design; D006860:Hydrogen Bonding; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D058909:Adenosine A3 Receptor Agonists; D043684:Receptor, Adenosine A3; D000241:Adenosine