Purine Receptors: GPCR Structure and Agonist Design

Various flexible and ring-constrained derivatives of adenosine that serve as A₃AR probes. N⁶ -(3-iodobenzyl)-5′-N-methylcarbamoyladenosine (IB-MECA)] and its 2-chloro analogue are widely used agonist probes. The full agonist MRS1898 is a conformationally-constrained (N)-methanocarba equivalent of Cl-IB-MECA. In the antagonist MRS1292, the 5′-amide moiety, which otherwise when freely flexible guaran-tees full agonism at the A₃ AR, is also conformationally constrained. K_i values (nM) in binding to human A₁, A_2A, and A₃ ARs and functional potency at the hA_2B AR are shown (30, 31, 35). See text for details.