Theoretical structure-activity studies of adenosine A1 ligands: requirements for receptor affinity.
The three-dimensional (3-D) requirements for A1 adenosine receptor affinity have been studied based on hydrogen-bonding functionality correlation between a group of twelve A1 adenosine receptor ligands representing ten structurally different classes of compounds. Electrostatic potential similarity indices and shape similarity indices strongly support the proposed receptor-bound orientations of the ligands. We conclude, in areas common to both agonist and antagonist binding at the A1 receptor, that the ligands are recognized by a similar physicochemical 3-D environment. The finding of similar 3-D requirements for agonists and antagonists suggests a fairly static receptor structure in the region common to agonist and antagonist binding. The ribose moiety is remote from antagonist binding site. Such a 3-D environment rationalizes the binding of a number of potent novel antagonists including KW-3902, not previously reported in modeling studies.
Dooley
M J
MJ
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, Shizuoka-ken, Japan.
Kono
M
M
Suzuki
F
F
D008024:Ligands; D008958:Models, Molecular; D008962:Models, Theoretical; D011485:Protein Binding; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008024:Ligands; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1