Platelet Aggregation Inhibitors. X. S-Substituted 2-Thioadenosines and Their Derivatives

A series of S-substituted 2-thioadenosines (IV) were prepared by treatment of 2-thioadenosine (III) with a requisite halide in NaOH-H2O, NaOH-H2O-EtOH, Na/dimeth-ylformamide, NaOMe/dimethylformamide or NaH/dimethylformamide. N-Substituted 2-aminoadenosines (V) were obtained by treatment of 2-chloroadenosine (II) with a requisite amine. Compounds (IV and V) and N-oxide derivatives of them were tested as inhibitors of adenosine 5'-diphosphate- and collagen-induced rabbit platelet aggregation. 2-Cycloalkyl- or 2-polycycloalkylthioadenosines (IV7-9), water-soluble 2-piperazino-ethylthioadenosines (IV16-19) and 2-thioadenosine N-oxide (X2) were found effective. Most of them showed long lasting activity during the incubation with rabbit plasma. Compounds (IV7-9) were also inhibitory against human platelet aggregation.