Design and synthesis of 3′-ureidoadenosine-5′-uronamides: Effects of the 3′-ureido group on binding to the A 3 adenosine receptor

Abstract

Novel 3′-ureidoadenosine analogues, 3 and 4 were synthesized from 1,2:5,6-di-O-isopropylidene-d-glucose in order to cause stronger hydrogen bonding than the corresponding 3′-aminoadenosine derivatives at the A 3 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. © 2004 Elsevier Ltd. All rights reserved.