MOLECULAR SIMULATION APPLIED TO 2-(N'-ALKYLIDENEHYDRAZINO)-ADENOSINE-A(2) AND 2-(N'-ARALKYLIDENEHYDRAZINO)ADENOSINE-A(2) AGONISTS

The planar double ring system of adenine is conformationally rigid. Ro tations of the ribose ring of adenosine around the N-glycosidic bond a re hindered by nonbonded electrostatic and steric forces. The flexibil ity of the sugar ring and the changed conformations of the substituent s of 2-(N'-allylidenehydrazino)- and 2-(N'-aralkylidenehydrazino)adeno sine A(2) agonists may be observed under changing solvent conditions a nd by energetic activation. Four hydrogen-bonding forces between the g lutarimide rings of a recently designed pseudoreceptor and the 'pharma cophoric groups' of the adenosine derivatives may be hypothesized. Str ucture-activity relationships show that the A(2) agonist potency is ma inly determined by the molar refraction of the substituents, the point -charge dipole moment of the molecule, and the type of substitution (a liphatic or aromatic groups).