The planar double ring system of adenine is conformationally rigid. Rotations of the ribose ring of adenosine around the N-glycosidic bond are hindered by nonbonded electrostatic and steric forces. The flexibility of the sugar ring and the changed conformations of the substituents of 2-(N'-alkylidenehydrazino)- and 2-(N'-aralkylidenehydrazino)adenosine A 2 agonists may be observed under changing solvent conditions and by energetic activation. Four hydrogen-bonding forces between the glutarimide rings of a recently designed pseudoreceptor and the 'pharmacophoric groups' of the adenosine derivatives may be hypothesized. Structure-activity relationships show that the A 2 agonist potency is mainly determined by the molar refraction of the substituents, the point-charge dipole moment of the molecule, and the type of substitution (aliphatic or aromatic groups).