1068147-87-4Relevant articles and documents
Synthesis of bivalent β2-adrenergic and adenosine A 1 receptor ligands
Karellas, Peter,McNaughton, Michael,Baker, Stephen P.,Scammells, Peter J.
experimental part, p. 6128 - 6137 (2009/10/01)
Research in the area of simutaneously targeting more than one G protein-coupled receptor (GPCR) has increased in recent times. By exploiting the cross talk between the β2-adrenergic (β2AR) and adenosine A1 receptors (A1AR) on adenylate cyclase activity, we synthesized a series of bivalent agonists for both GPCRs to generate responses from more than one receptor. We have demonstrated a relationship between the various β2-adrenergic and A1 adenosine bivalent parameters of linker and bifunctionality by using data that are drawn from in vitro assays. The hexyl-linked 12e (Ki, 311 nM) and butyl-linked 12c (Ki, 863 nM) bivalent compounds displayed reasonable binding affinities for the β2AR when compared with the control (-)isoproterenol (Ki, 136 nM), and both compounds also exhibited a persuasive bifunctional trend for both receptors at various drug concentrations. The bivalent compound 12e was also found to have significant EC50 potency (6 nM) at the β2AR in DDT cells.
