Structure Activity Relationships for Adenosine Agonists

Abstract

Adenosine elicits a wide variety of physiological responses (Williams, 1987) via interactions with two major subtypes of extracellular adenosine receptors, designated as A₁ and A₂. These two receptor subtypes can be distinguished on the basis of structure-activity relationships (Hamprecht et al., 1985) and have opposite effects on adenylate cyclase (Londos et al., 1980). With the advent of an A₂ binding assay (Bruns et al., 1986, Yeung et al., 1984), it has become possible to quantitatively evaluate the subtype selectivity of adenosine agonists. Recently, considerable effort has been devoted to the search for adenosine agonists with high selectivity for either A₁ or A₂ receptors. Our interest in adenosine receptors began with earlier disclosures that adenosine agonists such as R-PIA (Snyder et al., 1981), NECA (Prasad et al., 1980) or CV-1808 (Kawazoe et al., 1980) had potential utility as therapeutic agents (Figure 1). Thus, we set, out to develop structure-activity relationships (SAR) for both A₁ and A₂ receptors and especially to identify receptor selective agonists.