Inhibitors of adenosine deaminase. Studies in combining high-affinity enzyme-binding structural units. erythro-1,6-Dihydro-6-(hydroxymethyl)-9-(2-hydroxy-3-nonyl)purine and erythro-9-(2-hydroxy-3-nonyl)purine.

Article abstract of DOI:10.1021/jm00347a023

erythro-1,6-Dihydro-6-(hydroxymethyl)-9-(2-hydroxy-3-nonyl)purine (4) was synthesized as a potential adenosine deaminase inhibitor, which combines in a single molecule two structural moieties, each of which possesses high affinity to a different region of the enzyme, the catalytic region and an auxiliary binding region which is specific for erythro-9-(2-hydroxy-3-nonyl)adenine (1). The potency of 4 (Ki = 1.2 x 10(-5) M) is about one-seventeenth that of erythro-9-(2-hydroxy-3-nonyl)purine (2; Ki = 6.8 x 10(-7) M), which contains only one high-affinity moiety. The mutually interfering rather than reinforcing effects of the two moieties may indicate that lack of simultaneous binding and thus provide insight into the relative geometry of the two binding regions of the enzyme.